articles
The genome sequence of the plant pathogen Xylella fastidiosa The Xylella fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis*, Sa˜o Paulo, Brazil * A full list of authors appears at the end of this paper
............................................................................................................................................................................................................................................................................
Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis—a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We can assign putative functions to 47% of the 2,904 predicted coding regions. Efficient metabolic functions are predicted, with sugars as the principal energy and carbon source, supporting existence in the nutrient-poor xylem sap. The mechanisms associated with pathogenicity and virulence involve toxins, antibiotics and ion sequestration systems, as well as bacterium–bacterium and bacterium–host interactions mediated by a range of proteins. Orthologues of some of these proteins have only been identified in animal and human pathogens; their presence in X. fastidiosa indicates that the molecular basis for bacterial pathogenicity is both conserved and independent of host. At least 83 genes are bacteriophage-derived and include virulence-associated genes from other bacteria, providing direct evidence of phage-mediated horizontal gene transfer. Citrus variegated chlorosis (CVC), which was first recorded in Brazil in 1987, affects all commercial sweet orange varieties1. Symptoms include conspicuous variegations on older leaves, with chlorotic areas on the upper side and corresponding light brown lesions, with gum-like material on the lower side. Affected fruits are small, hardened and of no commercial value. A strain of Xylella fastidiosa was first identified as the causal bacterium in 1993 (ref. 2) and found to be transmitted by sharpshooter leafhoppers in 1996 (ref. 3). CVC control is at present limited to removing infected shoots by pruning, the application of insecticides and the use of healthy plants for new orchards. In addition to CVC, other strains of X. fastidiosa cause a range of economically important plant diseases including Pierce’s disease of grapevine, alfalfa dwarf, phony peach disease, periwinkle wilt and leaf scorch of plum, and are also associated with diseases in mulberry, pear, almond, elm, sycamore, oak, maple, pecan and coffee4. The triply cloned X. fastidiosa 9a5c, sequenced here, was derived from the pathogenic culture 8.1b obtained in 1992 in Bordeaux (France) from CVC-affected Valencia sweet orange twigs collected in Macaubal (Sa˜o Paulo, Brazil) on May 21, 1992 (ref. 2). Strain 9a5c produces typical CVC symptoms on inoculation into experimental citrus plants5, and into Nicotiana tabacum (S. A. Lopes, personal communication) and Catharantus roseus (P. BrantMonteiro, personal communication)—two novel experimental hosts.
General features of the genome The basic features of the genome are listed in Table 1 and a detailed map is shown in Fig. 1. The conserved origin of replication of the large chromosome has been identified in a region between the putative 50S ribosomal protein L34 and gyrB genes containing dnaA, dnaN and recF6. The Escherichia coli DnaA box consensus sequence TTATCCACA is found on both DNA strands close to dnaA. In addition, there are typical 13-nucleotide (ACCACCACCACCA) and 9-nucleotide (two TTTCATTGG and two TTTTATATT) sequences in other intergenic sequences of this region. This region is coincident with the calculated GC-skew signal inversion7. We have designated base 1 of the X. fastidiosa genome as the first Tof the only TTTTAT sequence found between the ribosomal protein L34 gene and dnaA. The overall percentage of open reading frames (ORFs) for which a putative biological function could be assigned (47%) was slightly below that for other sequenced genomes such as Thermotoga maritima8 (54%), Deinococcus radiodurans9 (52.5%) and Neisseria NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
meningitidis10 (53.7%). This may reflect the lack of previous complete genome sequences from phytopathogenic bacteria. Plasmid pXF1.3 contains only two ORFs, one of which encodes a replication-associated protein. Plasmid pXF51 contains 64 ORFs, of which 5 encode proteins involved in replication or plasmid stability and 20 encode proteins potentially involved in conjugative transfer. One ORF encodes a protein similar to the virulenceassociated protein D (VapD), found in many other bacterial pathogens11. Four regions of pXF51 present significant DNA similarity to parts of transposons found in plasmids from other bacteria, suggesting interspecific horizontal exchange of genetic material. The principal paralogous families are summarized in Table 2. The complete list of ORFs with assigned function is shown in Table 3. Seventy-five proteins present in the 21 completely sequenced genomes in the COG database12 (as of 15th March 2000) were also found in X. fastidiosa. Each of these sequences was used to Table 1 General features of the Xylella fastidiosa 9a5c genome Main chromosome Length (bp) G+C ratio Open reading frames (ORFs) Coding region (% of chromosome size) Average ORF length (bp) ORFs with functional assignment ORFs with matches to conserved hypothetical proteins ORFs without significant data base match Ribosomal RNA operons
tRNAs tmRNA
2,679,305 52.7% 2,782 88.0% 799 1,283 310 1,083 2 (16SrRNA-Ala-TGC-tRNA-Ile-GATtRNA-23SrRNA-5SrRNA) 49 (46 different sequences corresponding to all 20 amino acids) 1
.............................................................................................................................................................................
Plasmid pXF51 Length (bp) G+C ratio Open reading frames (ORFs) Protein coding region (% of plasmid size) ORFs with functional assignment ORFs with matches to conserved hypothetical proteins ORFs without significant data base match
51,158 49.6% 64 86.9% 30 8 24
.............................................................................................................................................................................
Plasmid pXF1.3 Length (bp) G+C ratio Open reading frames (ORFs) ORFs with functional assignment
1,285 55.6% 2 1
.............................................................................................................................................................................
© 2000 Macmillan Magazines Ltd
151
articles Table 2 Largest families of paralogous genes Family (total number of families = 312)
Number of genes (total number of genes = 853)
.............................................................................................................................................................................
ATP-binding subunits of ABC transporters Reductases/dehydrogenases Two-component system, regulatory proteins Hypothetical proteins Transcriptional regulators Fimbrial proteins Two-component system, sensor proteins
23 12 12 10 9 9 9
.............................................................................................................................................................................
generate a phylogenetic tree of the 22 organisms. In 69% of such trees, X. fastidiosa was grouped with Haemophilus influenzae and E. coli, consistent with a phylogenetic analysis undertaken with the 16S rRNA gene13. One ORF, a cytosine methyltransferase (XF1774), is interrupted by a Group II intron. The intron was identified on the basis of the presence of a reverse transcriptase-like gene (as in other Group II introns), conserved splice sites, conserved sequence in structure V and conserved elements of secondary structure14. Group II introns are rare in prokaryotes, but have been found in different evolutive lineages including E. coli, cyanobacteria and proteobacteria15.
Transcription, translation and repair The basic transcriptional and translational machinery of X. fastidiosa is similar to that of E. coli16. Recombinational repair, nucleotide and base-excision repair, and transcription-coupled repair are present with some noteworthy features. For example, no photolyase was found, indicating exclusively dark repair. Although the main genes of the SOS pathway, recA and lexA, are present, ORFs corresponding to the three DNA polymerases induced by SOS in E. coli (DNA polymerases II, IVand V)17 are missing, indicating that the mutational pathway itself may be distinct.
Energy metabolism Even though X. fastidiosa is, as its name suggests, a fastidious organism, energy production is apparently efficient. In addition to all the genes for the glycolytic pathway, all genes for the tricarboxylic acid cycle and oxidative and electron transport chains are present. ATP synthesis is driven by the resulting chemiosmotic proton gradient and occurs by an F-type ATP synthase. Fructose, mannose and glycerol can be utilized in addition to glucose in the glycolytic pathway. There is a complete pathway for hydrolysis of cellulose to glucose, consisting of 1,4-b-cellobiosidase, endo-1,4-b-glucanase and b-glucosidase, suggesting that cellulose breakdown may supplement the often low concentrations of monosaccharides in the xylem18. Two lipases are encoded in the genome, but there is no b-oxidation pathway for the hydrolysis of fatty acids, presumably precluding their utilization as an alternative carbon and energy source. Likewise, although enzymes required for the breakdown of threonine, serine, glycine, alanine, aspartate and glutamate are present, pathways for the catabolism of the other naturally occurring amino acids are incomplete or absent. The gluconeogenesis pathway appears to be incomplete. Phosphoenolpyruvate carboxykinase and the gluconeogenic enzyme fructose-1,6-bisphosphatase, which are required to bypass the irreversible step in glycolysis, are not present. The absence of the first is compensated by the presence of phosphoenolpyruvate synthase and malate oxidoreductase, which together can generate phosphoenolpyruvate from malate. There appears, however, to be no known compensating pathway for the absence of fructose-1,6bisphosphatase. It is possible that among the large number of unidentified X. fastidiosa genes there are non-homologous genes that compensate for steps in such critical pathways. Barring this possibility, however, the absence of a functional gluconeogenesis pathway implies a strict dependence on carbohydrates both as a 152
source of energy and anabolic precursors. The glyoxylate cycle is absent and the pentose phosphate pathway is incomplete. In the latter pathway, genes for neither 6-phosphogluconic dehydrogenase nor transaldolase were identified.
Small molecule metabolism X. fastidiosa exhibits extensive biosynthetic capabilities, presumably an absolute requirement for a xylem-dwelling bacterium. Most of the genes found in E. coli necessary for the synthesis of all amino acids from chorismate, pyruvate, 3-phosphoglycerate, glutamate and oxaloacetic acid16 were identified. However, some genes in X. fastidiosa are bi-functional, such as phosphoribosyl-AMP cyclohydrolase/phosphoribosyl-ATP pyrophosphatase (XF2213), aspartokinase/homoserine dehydrogenase I (XF2225), imidazoleglycerolphosphate dehydratase/histidinol-phosphate phosphatase (XF2217) and a new diaminopimelate decarboxylase/aspartate kinase (XF1116) that would catalyse the first and the last steps of lysine biosynthesis. In addition, the gene for acetylglutamate kinase (XF1001) has an acetyltransferase domain at its carboxy-terminal end that would compensate for the missing acetyltransferase in the arginine biosynthesis pathway. Other missing genes include phosphoserine phosphatase, cystathionine b-lyase, homoserine O-succinyltransferase and 2,4,5-methyltetrahydrofolate-homocysteine methyltransferase. The first two enzymes are also absent in the Bacillus subtilis genome, the third is absent in Haemophilus influenzae and the fourth is missing in both genomes12. We thus presume that alternative, unidentified enzymes complete the biosynthetic pathways in these organisms and in X. fastidiosa. The pathways for the synthesis of purines, pyrimidines and nucleotides are all complete. X. fastidiosa is also apparently capable of both synthesizing and elongating fatty acids from acetate. Again, however, some E. coli enzymes were not found, such as holo acylcarrier-protein synthase (also absent in Synechocystis sp., H. influenzae and Mycoplasma genitalium) and enoyl-ACP reductase (NADPH) (FabI) (also absent from M. genitalium, Borrelia burgdorferi and Treponema pallidum)12. X. fastidiosa appears to be capable of synthesizing an extensive variety of enzyme cofactors and prosthetic groups, including biotin, folic acid, pantothenate and coenzyme A, ubiquinone, glutathione, thioredoxin, glutaredoxin, riboflavin, FMN, FAD, pyrimidine nucleotides, porphyrin, thiamin, pyridoxal 59-phosphate and lipoate. In a number of the synthetic pathways, one or more of the enzymes present in E. coli are absent, but this is also true for at least one other sequenced Gram-negative bacterial genome in each case12. We therefore again infer that the missing enzymes are either not essential or replaced by unknown proteins with novel structures.
Transport-related proteins A total of 140 genes encoding transport-related proteins were identified, representing 4.8% of all ORFs. For comparison, E. coli, B. subtilis and M. genitalium have around 10% of genes encoding transport proteins, whereas Helicobacter pylori, Synechocystis sp. and Methanococcus jannaschii have 3.5–5.4% (ref. 19). Transport systems are central components of the host–pathogen relationship (Fig. 2). There are a number of ion transporters and transporters for the uptake of carbohydrates, amino acids, peptides, nitrate/nitrite, sulphate, phosphate and vitamin B12. Many different transport
Figure 1 Linear representation of the main chromosome and plasmids pXF51 and Q pXF1.3 of the Xylella fastidiosa genome. Genes are coloured according to their biological role. Arrows indicate the direction of transcription. Genes with frameshift and point mutations are indicated with an X. Ribosomal RNA genes, the tmRNA, the principal repeats, prophages and the group II intron are indicated by coloured lines. Transfer RNAs are identified by a single letter identifying the amino acid. Pie chart represents the distribution of the number of genes according to biological role. The numbers below protein-producing genes correspond to gene IDs.
© 2000 Macmillan Magazines Ltd
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
articles families are represented and include both small and large mechanosensitive conductance ion channels, a monovalent cation:proton antiporter (CAP-2) and a glycerol facilitator belonging to the major intrinsic protein (MIP) family. In addition, 23 ABC transport systems comprising 41 genes can be identified. X. fastidiosa appears to possess a phosphotransferase system (PTS) that typically mediates small carbohydrate uptake. There are both the enzyme I and HPr components of this system, as well as a gene supposedly involved in its regulation (pstK or hprK); however, there is no PTS permease—an essential component of the phosphotransferase complex. The functionality of the system therefore remains in question. There are five outer membrane receptors, including siderophores, ferrichrome-iron and haemin receptors, which are all associated with iron transport. The energizing complexes, TonB–ExbB–ExbD and the paralogous TolA–TolR–TolQ, essential for the functioning of the outer membrane receptors, are also present. In all, 67 genes encode proteins involved in iron metabolism. We propose that in X. fastidiosa the uptake of iron and possibly of other transition metal ions such as manganese causes a reduction in essential micronutrients in the plant xylem, contributing to the typical symptoms of leaf variegation. The X. fastidiosa genome encodes a battery of proteins that mediate drug inactivation and detoxification, alteration of potential drug targets, prevention of drug entry and active extrusion of drugs and toxins. These include ABC transporters and transport processes driven by a proton gradient. Of the latter, eight belong to the hydrophobe/amphiphile efflux-1 (HAE1) family, which act as multidrug resistance factors.
system controlling transcription of fimbrial subunits, presumably in response to host cues, and pilG, H, I, J and chpA, which encode a chemotactic system transducing environmental signals to the pilus machinery. In addition to the EPS and fimbriae, which are likely to have central roles in the clumping of bacteria and in adhesion to the xylem walls, we also identified outer membrane protein homologues for afimbrial adhesins. Although fimbrial adhesins are well characterized as crucial virulence factors in both plant and human pathogens25, afimbrial adhesins, which are directly associated with the bacterial cell surface, have been hitherto associated only with human and animal pathogens, where they promote adherence to epithelial tissue. Of the three putative adhesins of this kind identified in X. fastidiosa, two exhibit significant similarity to each other (XF1981, XF1529) and to the hsf and hia gene products of H. influenzae26. The third (XF1516) is similar to the uspA1 gene product of Moraxella catarrhalis27. All these proteins share the common C-terminal domain of the autotransporter family28. Direct experimentation will be required to establish whether these adhesins promote binding to plant cell structures or components of the insect vector foregut, or both. Nevertheless, their presence in the X. fastidiosa genome adds to the increasing evidence for the generality of mechanisms of bacterial pathogenicity, irrespective of the host organism29. We also identified three different haemagglutinin-like genes. Again, similar genes have not previously been identified in plant pathogens. These genes (XF2775, XF2196, XF0889) are the largest in the genome and exhibit highest similarity to a Neisseria meningitidis putative secreted protein10.
Adhesion
Intervessel migration
X. fastidiosa is characteristically observed embedded in an extracellular translucent matrix in planta20. Clumps of bacteria form within the xylem vessels leading to their blockage and symptoms of the disease such as water-stress leaf curling. We deduce, from our analysis of the complete genome sequence, that the matrix is composed of extracellular polysaccharides (EPSs) synthesized by enzymes closely related to those of Xanthomonas campestris pv campestris (Xcc) that produce what is commercially known as xanthan gum. In comparison with Xcc, however, we did not find gumI (encoding glycosyltransferase V, which incorporates the terminal mannose), gumL (encoding ketalase which adds pyruvate to the polymer) or gumG (encoding acetyltransferase which adds acetate), suggesting that Xylella gum may be less viscous than its Xanthomonas counterpart. Positive regulation of the synthesis of extracelullar enzymes and EPS in Xanthomomas is effected by proteins coded by the rpf (regulation of pathogenicity factors) gene cluster21. Mutations in any of these genes in Xanthomomas results in failure to synthesize the EPS. In consequence, the strain becomes non-pathogenic21. X. fastidiosa contains genes that encode RpfA, RpfB, RpfC and RpfF, suggesting that both bacteria may regulate the synthesis of pathogenic EPS factors through similar mechanisms. Fimbria-like structures are readily apparent upon electron microscopical observation of X. fastidiosa within both its plant and insect hosts22. Because of the high velocity of xylem sap passing through narrow portions of the insect foregut, fimbria-mediated attachment may be essential for insect colonization. Indeed, in the insect mouthparts the bacteria are attached in ordered arrays, indicating specific and polarized adhesion23. In addition, fimbriae are thought to be involved in both plant–bacterium and bacterium–bacterium interactions during colonization of the xylem itself. We identified 26 genes encoding proteins responsible for the biogenesis and function of Type 4 fimbria filaments. This type of fimbria is found at the poles of a wide range of bacterial pathogens where they act to mediate adhesion and translocation along epithelial surfaces24. The genes include pilS and pilR homologues, which encode a two-component
Movement between individual xylem vessels is crucial for effective colonization by X. fastidiosa. For this to occur, degradation of the pit membrane of the xylem vessel is required. Of the known pectolytic enzymes capable of this function, a polygalacturonase precursor and a cellulase were identified, although the former contains an authentic frameshift. These genes exhibited highest similarity to orthologues in Ralstonia solanacearum—which causes wilt disease in tomatoes—where the polygalacturonase genes are required for wild-type virulence.
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
Toxicity We identified five haemolysin-like genes: haemolysin III (XF0175), which belongs to an uncharacterized protein family, and four others (XF0668, XF1011, XF2407, XF2759) which belong to the RTX toxin family that contains tandemly repeated glycine-rich nonapeptide motifs at the C-terminal domain. One of these ORFs is closely related to bacteriocin, an RTX toxin also found in the plant bacterium Rhizobium leguminosarum30. RTX or RTX-like proteins are important virulence factors widely distributed among Gramnegative pathogenic bacteria31. There are two Colicin-V-like precursor proteins. Colicin V is an antibacterial polypeptide toxin produced by E. coli, which acts against closely related sensitive bacteria32. The precursors consist of 102-amino-acid peptides (XF0262, XF0263) that have the typical conserved leader 15-amino-acid motif, and have some similarity with Colicin V from E. coli at the remaining C-terminal portion. The necessary apparatus for Colicin biosynthesis and secretion is also present. Interestingly, in E. coli most of the genes necessary for biogenesis and export of Colicin V are in a gene cluster present in a plasmid, whereas in X. fastidiosa these genes are dispersed in the chromosome. We found four genes that may function in polyketide biogenesis: polyketide synthase (PKS), pteridine-dependent deoxygenase, daunorubicin C-13 ketoreductase and a NonF-related protein. These genes belong to the synthesis pathways of frenolicin, rapamycin, daunorubicin and nonactin, respectively. These pathways
© 2000 Macmillan Magazines Ltd
153
articles
Figure 2 A comprehensive view of the biochemical processes involved in Xylella fastidiosa pathogenicity and survival in the host xylem. The principal functional categories are shown in bold, and the bacterial genes and gene products related to that function are arranged within the coloured section containing the bold heading. Transporters are indicated as follows: cylinders, channels; ovals, secondary carriers, including the MFS family; paired dumbbells, secondary carriers for drug extrusion; triple dumbbells, ABC transporters; bulb-like icon, F-type ATP synthase; squares, other transporters. Icons with two arrows 154
represent symporters and antiporters (H+ or Na+ porters, unless noted otherwise). 2,5DDOL, 2,5-dichloro-2,5-cyclohexadiene-1,4-dol; EPS, exopolysaccharides; MATE, multi-antimicrobial extrusion family of transporters multidrug efflux gene (XF2686); MFS, major facilitator superfamily of transporters; Pbp, b-lactamase-like penicillin-binding protein (XF1621); RND, resistance-nodulation-cell division superfamily of transporters; ROS, reactive oxygen species.
© 2000 Macmillan Magazines Ltd
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
articles include many more enzymes, which we did not find; however, some of the genes listed lie close to ORFs without significant database matches, suggesting that at least one (as yet undiscovered) polyketide pathway may be functional.
Prophages Bacteriophages can mediate the evolution and transfer of virulence factors and occasional acquisition of new traits by the bacterial host. Because as much as 7% of the X. fastidiosa genome sequenced corresponds to double-stranded (ds) DNA phage sequences, mostly from the Lambda group, we suspect that this route may have been of particular importance for this bacterium. It is noteworthy that a very high percentage of phage-related sequences has also been detected in a second vascular-restricted plant pathogen, Spiroplasma citri33. We identified four regions, with a high density of ORFs homologous to phage sequences, that we considered to be prophages, in addition to isolated phage sequences dispersed throughout the genome. Two of these prophages (each ,42 kbp, designated XfP1 and XfP2) are similar to each other, lie in opposite orientations in distinct regions and appear to belong to the dsDNA, tailed-phage group. Both appear to contain most of the genes responsible for particle assembly, although we know of no reports of phage particle release from X. fastidiosa cultures. In prophage XfP1, we found two ORFs between tail genes V and W that are similar to ORF118 and vapA from the virulence-associated region of the animal pathogen Dichelobacter nodosus, which by homology encode a killer and a suppressor protein34. Interestingly, in prophage XfP2, we found two other ORFs also between tail genes V and W that are similar to hypothetical ORFs of Ralstonia eutropha transposon Tn4371 (ref. 35). The other two identified prophages, XfP3 and XfP4, are also similar in sequence to each other and to the H. influenzae cryptic prophage fflu (ref. 36). They both contain a 14,317-bp exact repeat. Few particle-assembly genes were found in these regions, suggesting that these prophages are defective. An ORF similar to hicB from H. influenzae, a component of the major pilus gene cluster in some isolates, was found in XfP4 (ref. 37). The presence of virulence-associated genes from other organisms within the prophage sequences is strong evidence for a direct role for bacteriophage-mediated horizontal gene transfer in the definition of the bacterial phenotype.
Absence of avirulence genes Phytopathogenic bacteria generally have a limited host range, often confined to members of a single species or genus. This specificity is defined by the products of the so-called avirulence (avr) genes present in the pathogen, which are injected directly into host cells, on infection, through a type III secretory system38–40. BLAST41 searches with all known avr and type III secretory system sequences failed to identify genes encoding proteins with significant similarities in the genome of X. fastidiosa. Although the variability of avr genes amongst bacteria might account for this apparent lack, the high level of similarity of some components of the type III secretory system argues against this. We suspect that these genes are, in fact, not required because of the insect-mediated transmission and vascular restriction of the bacterium that obviates the necessity of host cell infection. Furthermore, if the differing host ranges of X. fastidiosa are molecularly defined, this may be by a quite different mechanism not involving avr proteins.
Conclusions Before the elucidation of its complete genome sequence, very little was known of the molecular mechanisms of X. fastidiosa pathogenicity. Indeed, this bacterium was probably the least characterized of all organisms that have been fully sequenced. Our complete genetic analysis has determined not only the basic metabolic and replicative characteristics of the bacterium, but also a number of potential NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
pathogenicity mechanisms. Some of these have not previously been postulated to occur in phytopathogens, providing new insights into the generality of these processes. Indeed, the availability of this first complete plant pathogen genome sequence will now allow the initiation of the detailed comparison of animal and plant pathogens at the whole-genome level. In addition, the information contained in the sequence should provide the basis for an accelerated and rational experimental dissection of the interactions between X. fastidiosa and its hosts that might lead to fresh insights into M potential approaches to the control of CVC.
Methods The sequencing and analysis in this project were carried out by a network of 34 biology laboratories and one bioinformatics centre. The network is called the Organization for Nucleotide Sequencing and Analysis (ONSA)42, and is entirely located in the state of Sa˜o Paulo, Brazil.
Sequencing and assembly The sequence was generated using a combination of ordered cosmid and shotgun strategies43. A cosmid library was constructed, providing roughly 15-fold genome coverage, containing 1,056 clones with average insert size of 40 kilobases (kb). High-density colony filters of the library were made, and a physical map of the genome was constructed using a strategy of hybridization without replacement44. A total of 113 cosmid clones was selected for sequencing on the basis of the hybridization map and end-sequence analysis. The cosmid sequences were assembled into 15 contigs covering 90% of the genome. Additionally, shotgun libraries with different insert sizes (0.8–2.0 kb and 2.0–4.5 kb) were constructed from nebulized or restricted genomic DNA cloned into plasmids, and sequenced to achieve a 3.74-fold coverage of high-quality sequence (29,140 reads). Most of the sequencing was performed with BigDye terminators on ABI Prism 377 DNA sequencers. Cosmid and shotgun sequences were assembled into six contigs. We identified sequence gaps by linking information from forward and reverse reads, and closed either by primer walking or insert subcloning. The remaining physical gaps were closed by combinatorial PCR and by lambda clones selected from a lDash library by end-sequencing. The collinearity between the genome and the obtained sequence was confirmed by digestion of genomic DNA with AscI, NotI, SfiI, SmiI and SrfI, followed by comparison of the digestion pattern with the electronic digestion of the generated sequence. In addition, sequences from both ends of most cosmid clones and 236 l clones were used to confirm the orientation and integrity of the contigs. The sequence was assembled using phred+phrap+consed45. All consensus bases have quality with Phred value of at least 20. There are no unexplained high quality discrepancies, each consensus base is confirmed by at least one read from each strand, and the overall error estimate is less than 1 in every 10,000 bases.
ORF prediction and annotation ORFs were determined using glimmer 2.0 (ref. 46) and the glimmer post-processor RBSfinder (S. L. Salzberg, personal communication). A few ORFs were found by hand guided by BLAST41 results. Annotation was carried out in a cooperative way, mostly by comparison with sequences in public databases, using BLAST41 and tRNAscan-SE (ref. 47) and was based on the functional categories for E. coli48. Only one tmRNA was located (K. Williams, personal communication). To help annotate transport proteins, we built a custom BLAST41 database using sequences from http://www-biology.ucsd.edu/,msaier/ transport/toc.html and compared our ORFs with these sequences. Phylogenetic trees for conserved COGs12 were built using ClustalX49 for multiple alignment and Phylip50. Paralogous gene families (Table 2) were determined using BLASTX with the E-value cut-off equal to e-5 and such that at least 60% of the query sequence and at least 30% of the subject sequence were aligned. Received 24 March; accepted 24 May 2000. 1. Rosseti, V. et al. Pre´sence de bacte´ries dans le xyle`me d’orangers atteints de chlorose varie´ge´e, une nouvelle maladie des agrumes au Bre´sil. C. R. Acad. Sci. Paris se´rie III, 310, 345–349 (1990). 2. Chang, C. J. et al. Culture and serological detection of the xylem-limited bacterium causing citrus variegated chlorosis and its identification as a strain of Xylella fastidiosa. Curr. Microbiol. 27, 137–142 (1993). 3. Roberto, S. R., Coutinho, A., De Lima, J. E. O., Miranda, V. S. & Carlos, E. F. Transmissa˜o de Xylella fastidiosa pelas cigarrinhas Dilobopterus costalimai, Acrogonia terminalis e Oncometopia facialis em citros. Fitopatol. Bras. 21, 517–518 (1996). 4. Purcell, A. H. & Hopkins, D. L. Fastidious xylem-limited bacterial plant pathogens. Annu. Rev. Phytopathol. 34, 131–151 (1996). 5. Li, W. B. et al. A triply cloned strain of Xylella fastidiosa multiplies and induces symptoms of citrus variegated chlorosis in sweet orange. Curr. Microbiol. 39, 106–108 (1999). 6. Ye, F., Renaudin, J., Bove´, J. M. & Laigret, F. Cloning and sequencing of the replication origin (oriC) of the Spiroplasma citri chromosome and construction of autonomously replicating artificial plasmids. Curr. Microbiol. 29, 23–29 (1994). 7. Francino, M. P. & Ochman, H. Strand asymmetries in DNA evolution. Trends Genet. 13, 240–245 (1997). 8. Nelson, K. E. et al. Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature 399, 323–329 (1999).
© 2000 Macmillan Magazines Ltd
155
articles 9. White, O. et al. Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1. Science 286, 1571–1577 (1999). 10. Tettelin, H. et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809–1815 (2000). 11. Katz, M. E., Strugnell, R. A. & Rood, J. I. Molecular characterization of a genomic region associated with virulence in Dichelobacter nodosus. Infect. Immun. 60, 4586–4592 (1992). 12. Tatusov, R. L., Galperin, M. Y., Natale, D. A. & Koonin, E. V. The COG database: a tool for genome scale analysis of protein functions and evolution. Nucleic Acids Res. 28, 33–36 (2000). 13. Preston, G. M., Haubold, B. & Rainey, P. B. Bacterial genomics and adaptation to life on plants: implications for the evolution of pathogenicity and symbiosis. Curr. Opin. Microbiol. 1, 589–597 (1998). 14. Knoop, V., Kloska, S. & Brennicke, A. On the identification of group II introns in nucleotide sequence data. J. Mol. Biol. 242, 389–396 (1994). 15. Ferat, J. L. & Michel, F. Group II self-splicing introns in bacteria. Nature 364, 358–361 (1993). 16. Blattner, F. R. et al. The complete genome sequence of Escherichia coli K-12. Science 277, 1453–1474 (1997). 17. Bridges, B. A. DNA repair: Polymerases for passing lesions. Curr. Biol. 9, R475–R477 (1999). 18. Brodbeck, B. V., Andersen, P. C. & Mizell, R. F. Effects of total dietary nitrogen and nitrogen form on the development of xylophagous leafhoppers. Arch. Insect Biochem. Physiol. 42, 37–50 (1999). 19. Paulsen, I. T., Sliwinski, M. K. & Saier, M. H. J. Microbial genome analyses: global comparisons of transport capabilities based on phylogenies, bioenergetics and substrate specificities. J. Mol. Biol. 277, 573–592 (1998). 20. Chagas, C. M., Rossetti, V. & Beretta, M. J. G. Electron-microscopy studies of a xylem-limited bacterium in sweet orange affected with citrus variegated chlorosis disease in Brazil. J. Phytopathol. 134, 306–312 (1992). 21. Tang, J. L. et al. Genetic and molecular analysis of a cluster of rpf genes involved in positive regulation of synthesis of extracellular enzymes and polysaccharide in Xanthomonas campestris pathovar campestris. Mol. Gen. Genet. 226, 409–417 (1991). 22. Raju, C. B. & Wells, J. M. Diseases caused by fastidious xylem-limited bacteria. Plant Disease 70, 182– 186 (1986). 23. Brlansky, R. H., Timmer, I. W., French, W. J. & McCoy, R. E. Colonization of the sharpshooter vectors, Oncometopia igricans and Homalodisca coagulata, by xylem-limited bacteria. Phytopathology 73, 530– 535 (1983). 24. Fernandez, L. A. & Berenguer, J. Secretion and assembly of regular surface structures in Gram-negative bacteria. FEMS Microbiol. Rev. 24, 21–44 (2000). 25. Soto, G. E. & Hultgren, S. J. Bacterial adhesins: common themes and variations in architecture and assembly. J. Bacteriol. 181, 1059–1071 (1999). 26. Geme, J. W. Molecular determinants of the interaction between Haemophilus influenzae and human cells. Am. J. Respir. Crit. Care Med. 154, S192–S196 (1996). 27. Cope, L. D. et al. Characterization of the Moraxella catarrhalis uspA1 and uspA2 genes and their encoded products. J. Bacteriol. 181, 4026–4034 (1999). 28. Henderson, I. R., Navarro-Garcia, F. & Nataro, J. P. The great escape: structure and function of the autotransporter proteins. Trends Microbiol. 6, 370–378 (1998). 29. Rahme, L. G. et al. Common virulence factors for bacterial pathogenicity in plants and animals. Science 268, 1899–1902 (1995). 30. Oresnik, I. J., Twelker, S. & Hynes, M. F. Cloning and characterization of a Rhizobium leguminosarum gene encoding a bacteriocin with similarities to RTX toxins. Appl. Environ. Microbiol. 65, 2833–2840 (1999). 31. Lally, E. T., Hill, R. B., Kieba, I. R. & Korostoff, J. The interaction between RTX toxins and target cells. Trends Microbiol. 7, 356–361 (1999). 32. Havarstein, L. S., Holo, H. & Nes, I. F. The leader peptide of colicin V shares consensus sequences with leader peptides that are common among peptide bacteriocins produced by gram-positive bacteria. Microbiology 140, 2383–2389 (1994). 33. Ye, F. et al. A physical and genetic map of the Spiroplasma citri genome. Nucleic Acids Res. 20, 1559– 1565 (1992). 34. Billington, S. J., Johnston, J. L. & Rood, J. I. Virulence regions and virulence factors of the ovine footrot
pathogen, Dichelobacter nodosus. FEMS Microbiol. Lett. 145, 147–156 (1996). 35. Merlin, C., Springael, D. & Toussaint, A. Tn4371: A modular structure encoding a phage-like integrase, a Pseudomonas-like catabolic pathway, and RP4/Ti-like transfer functions. Plasmid 41, 40– 54 (1999). 36. Hendrix, R. W., Smith, M. C., Burns, R. N., Ford, M. E. & Hatfull, G. F. Evolutionary relationships among diverse bacteriophages and prophages: All the world’s a phage. Proc. Natl Acad. Sci. USA 96, 2192–2197 (1999). 37. Mhlanga-Mutangadura, T., Morlin, G., Smith, A. L., Eisenstark, A. & Golomb, M. Evolution of the major pilus gene cluster of Haemophilus influenzae. J. Bacteriol. 180, 4693–4703 (1998). 38. Alfano, J. R. & Collmer, A. The type III (Hrp) secretion pathway of plant pathogenic bacteria: trafficking harpins, Avr proteins, and death. J. Bacteriol. 179, 5655–5662 (1997). 39. Galan, J. E. & Collmer, A. Type III secretion machines: bacterial devices for protein delivery into host cells. Science 284, 1322–1328 (1999). 40. Young, G. M., Schmiel, D. H. & Miller, V. L. A new pathway for the secretion of virulence factors by bacteria: the flagellar export apparatus functions as a protein-secretion system. Proc. Natl Acad. Sci. USA 96, 6456–6461 (1999). 41. Altschul, S. F. et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 25, 3389–3402 (1997). 42. Simpson, A. J. & Perez, J. F. ONSA, the Sa˜o Paulo Virtual Genomics Institute. Nature Biotechnol. 16, 795–796 (1998). 43. Fleischmann, R. D. et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269, 496–512 (1995). 44. Hoheisel, J. D. et al. High resolution cosmid and P1 maps spanning the 14 Mb genome of the fission yeast S. pombe. Cell 73, 109–120 (1993). 45. Gordon, D., Abajian, C. & Green, P. Consed: a graphical tool for sequence finishing. Genome Res. 8, 195–202 (1998). 46. Delcher, A. L., Harmon, D., Kasif, S., White, O. & Salzberg, S. L. Improved microbial gene identification with GLIMMER. Nucleic Acids Res. 27, 4636–4641 (1999). 47. Lowe, T. M. & Eddy, S. R. tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequences. Nucleic Acids Res. 25, 955–964 (1997). 48. Riley, M. Functions of the gene products of Escherichia coli. Microbiol. Rev. 57, 862–952 (1993). 49. Thompson, J. D., Gibson, T. J., Plewniak, F., Jeanmougin, F. & Higgins, D. G. The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 25, 4876–4882 (1997). 50. Felsenstein, J. PHYLIP—Phylogeny Inference Package (Version 3. 2). Cladistics 5, 164–166 (1989).
Supplementary information is available on Nature’s World-Wide Web site (http://www.nature.com), or on the author’s World-Wide Web site (http://www.lbi.ic.unicamp.br/xf) or as paper copy from the London editorial office of Nature.
Acknowledgements The consortium is indebted to J. F. Perez, Scientific Director of Fundac¸a˜o de Amparo a` Pesquisa do Estado de Sa˜o Paulo (FAPESP), for his strategic vision in creating and nurturing this project as well as C. A. de Pian and Juc¸ara Parra for their administrative coordination. We thank our Steering Committee: S. Oliver, A. Goffeau, J. Sgouros, A. C. M. Paiva and J. L. Azevedo for their critical accompaniment of the work. We also thank R. Fulton and P. Minx for their timely contribution and advice. Project funding was from FAPESP, the RHAE programme of the Conselho Nacional de Desenvolvimento Cientı´fico e Tecnolo´gico (CNPq) and Fundecitrus. For the full list of individuals who contributed to the completion of this project see (http://www.lbi. ic.unicamp.br/xf). Correspondence and requests for materials should be addressed to J.C.S. (e-mail:
[email protected]). The sequence has been deposited in GenBank with accession numbers AE003849 (chromosome), AE003850 (pXF1.3) and AE003851 (pXF51).
Authors: A. J. G. Simpson1, F.C. Reinach2, P. Arruda3, F. A. Abreu4, M. Acencio5, R. Alvarenga2, L. M. C. Alves6, J. E. Araya7, G. S. Baia2, C. S. Baptista8, M. H. Barros8, E. D. Bonaccorsi2, S. Bordin9, J. M. Bove´10, M. R. S. Briones7, M. R. P. Bueno11, A. A. Camargo1, L. E. A. Camargo12, D. M. Carraro12, H. Carrer12, N. B. Colauto13, C. Colombo14, F. F. Costa9, M. C. R. Costa15, C. M. Costa-Neto16, L. L. Coutinho12, M. Cristofani17, E. Dias-Neto1, C. Docena2, H. El-Dorry2, A. P. Facincani6, A. J. S. Ferreira2, V. C. A. Ferreira18, J. A. Ferro6, J. S. Fraga4, S. C. Franc¸a19, M. C. Franco20, M. Frohme21, L. R. Furlan22, M. Garnier10, G. H. Goldman23, M. H. S. Goldman24, S. L. Gomes2, A. Gruber4, P. L. Ho25, J. D. Hoheisel21, M. L. Junqueira26, E. L. Kemper3, J. P. Kitajima27, J. E. Krieger26, E. E. Kuramae28, F. Laigret10, M. R. Lambais12, L. C. C. Leite25, E. G. M. Lemos6, M. V. F. Lemos29, S. A. Lopes19, C. R. Lopes13, J. A. Machado30†, M. A. Machado17, A. M. B. N. Madeira4, H. M. F. Madeira12†, C. L. Marino13, M. V. Marques8, E. A. L. Martins25, E. M. F. Martins18, A. Y. Matsukuma2, C. F. M. Menck8, E. C. Miracca5, C. Y. Miyaki11, C. B. Monteiro-Vitorello12, D. H. Moon20, M. A. Nagai5, A. L. T. O. Nascimento25, L. E. S. Netto11, A. Nhani Jr6, F. G. Nobrega8†, L. R. Nunes31, M. A. Oliveira32, M. C. de Oliveira33, R. C. de Oliveira31, D. A. Palmieri13, A. Paris13, B. R. Peixoto2, G. A. G. Pereira32, H. A. Pereira Jr6, J. B. Pesquero16, R. B. Quaggio2, P. G. Roberto19, V. Rodrigues34, A. J. de M. Rosa34, V. E. de Rosa Jr28, R. G. de Sa´34, R. V. Santelli2, H. E. Sawasaki14, A. C. R. da Silva2, A. M. da Silva2, F. R. da Silva3,27, W. A. Silva Jr15, J. F. da Silveira7, M. L. Z. Silvestri2, W. J. Siqueira14, A. A. de Souza17, A. P. de Souza3, M. F. Terenzi23, D. Truffi12, S. M. Tsai20, M. H. Tsuhako18, H. Vallada35, M. A. Van Sluys33, S. Verjovski-Almeida2, A. L. Vettore3, M. A. Zago15, M. Zatz11, J. Meidanis27 & J. C. Setubal27. Addresses: 1, Instituto Ludwig de Pesquisa sobre o Caˆncer, Rua Prof. Antonio Prudente,109 – 4o andar, 01509-010, Sa˜o Paulo - SP, Brazil; 2, Departamento de Bioquı´ mica, Instituto de Quı´ mica, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes, 748, 05508-900, Sa˜o Paulo SP, Brazil; 3, Centro de Biologia Molecular e Engenharia Gene´tica, Universidade Estadual de Campinas, Caixa Postal 6010,13083-970, Campinas – SP, Brazil; 4, Laborato´rio de Biologia Molecular, Departamento de Patologia, Faculdade de Medicina Veterina´ria e Zootecnia, Universidade de Sa˜o Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, 05508-000, Sa˜o Paulo – SP, Brazil; 5, Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina, Universidade de Sa˜o Paulo, Av. Dr. Arnaldo, 455, 01296-903, Sa˜o Paulo – SP, Brazil; 6, Departamento de Tecnologia, Faculdade de Cieˆncias Agra´rias e Veterina´rias de Jaboticabal, Universidade Estadual Paulista, Via 156
© 2000 Macmillan Magazines Ltd
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
articles de Acesso Prof. Paulo D. Castellane s/n, Km 5,14884-900, Jaboticabal – SP, Brazil; 7, Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de Sa˜o Paulo, Rua Botucatu, 862, 04023-062, Sa˜o Paulo – SP, Brazil; 8, Departamento de Microbiologia, Instituto de Cieˆncias Biome´dicas, Universidade de Sa˜o Paulo, Av. Prof. Lineu Prestes,1374, 05508-900, Sa˜o Paulo – SP, Brazil; 9, Hemocentro, Faculdade de Cieˆncias Me´dicas, Universidade Estadual de Campinas,13083-97, Campinas – SP, Brazil; 10, Institut National de la Recherche Agronomique et Universite´ Victor Se´galen Bordeaux 2, 71 Avenue Edouard Bourleaux, Laboratoire de Biologie Cellulaire et Mole´culaire, 33883 Vilenave d’Ornon Cedex, France; 11, Departamento de Biologia, Instituto de Biocieˆncias, Universidade de Sa˜o Paulo, Rua do Mata˜o, 277, 05508-900, Sa˜o Paulo – SP, Brazil; 12, Escola Superior de Agricultura Luiz de Queiroz, Universidade de Sa˜o Paulo, Av. Pa´dua Dias,11,13418-900, Piracicaba – SP, Brazil; 13, Departamento de Gene´tica, Instituto de Biocieˆncias, Universidade Estadual Paulista, Distrito de Rubia˜o Junior,18618-000, Botucatu – SP, Brazil; 14, Centro de Gene´tica, Biologia Molecular e Fitoquı´ mica, Instituto Agronoˆmico de Campinas, Av. Bara˜o de Itapura,1481, Caixa Postal 28,13001-970, Campinas – SP, Brazil; 15, Departamento de Clı´ nica Me´dica, Faculdade de Medicina de Ribeira˜o Preto, Universidade de Sa˜o Paulo, Av. Bandeirantes, 3900,14049-900, Ribeira˜o Preto – SP, Brazil; 16, Departamento de Biofı´ sica, Escola Paulista de Medicina, Universidade Federal de Sa˜o Paulo, Rua Botucatu, 862, 04023-062, Sa˜o Paulo – SP, Brazil; 17, Centro de Citricultura Sylvio Moreira, Instituto Agronoˆmico de Campinas, Caixa Postal 04,13490-970, Cordeiro´polis – SP, Brazil; 18, Laborato´rio de Bioquı´ mica Fitopatolo´gica e Laborato´rio de Imunologia, Instituto Biolo´gico, Av. Cons. Rodrigues Alves,1252, 04014-002, Sa˜o Paulo – SP, Brazil; 19, Departamento de Biotecnologia de Plantas Medicinais, Universidade de Ribeira˜o Preto, Av. Costa´bile Romano, 2201,14096-380, Ribeira˜o Preto – SP, Brazil; 20,Centro de Energia Nuclear na Agricultura, Universidade de Sa˜o Paulo, Av. Centena´rio, 303, Caixa Postal 96,13400-970, Piracicaba – SP, Brazil; 21, Funktionelle Genomanalyse, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 506, D-69120, Heidelberg, Germany; 22, Departamento de Melhoramento e Nutric¸a˜o Animal, Faculdade de Medicina Veterina´ria e Zootecnia, Universidade Estadual Paulista, Fazenda Lageado, Caixa Postal 560,18600-000, Botucatu - SP, Brazil; 23, Departamento de Cieˆncias Farmaceˆuticas , Faculdade de Cieˆncias Farmaceˆuticas de Ribeira˜o Preto, Universidade de Sa˜o Paulo, Av. do Cafe´ s/n,14040-903, Ribeira˜o Preto – SP, Brazil; 24, Departamento de Biologia, Faculdade de Filosofia, Cieˆncias e Letras de Ribeira˜o Preto, Universidade de Sa˜o Paulo, Av. Bandeirantes, 3900,14040-901, Ribeira˜o Preto – SP, Brazil; 25, Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil,1500, 05503-900, Sa˜o Paulo – SP, Brazil; 26, Laborato´rio de Gene´tica e Cardiologia Molecular/LIM 13, Instituto do Corac¸a˜o (InCor), Faculdade de Medicina, Universidade de Sa˜o Paulo, Av. Dr. Ene´as de Carvalho Aguiar, 44, 05403-000, Sa˜o Paulo – SP, Brazil; 27, Instituto de Computac¸a˜o, Universidade Estadual de Campinas, Caixa Postal 6176,13083-970, Campinas – SP, Brazil; 28, Departamento de Produc¸a˜o Vegetal, Faculdade de Cieˆncias Agronoˆmicas, Universidade Estadual Paulista, Fazenda Lageado, Caixa Postal 237,18603-970, Botucatu – SP, Brazil; 29, Departamento de Biologia Aplicada a` Agropecua´ria, Faculdade de Cieˆncias Agra´rias e Veterina´rias de Jaboticabal, Universidade Estadual Paulista, Via de Acesso Prof. Paulo Donato Castellane,14884-900, Jaboticabal – SP, Brazil; 30, Hospital do Caˆncer – A.C. Camargo, R. Antonio Prudente, 211, 01509-010, Sa˜o Paulo – SP, Brazil; 31, Nu´cleo Integrado de Biotecnologia, Universidade de Mogi das Cruzes, Av. Dr. Caˆndido Xavier de Almeida Souza, 200, 08780-911, Mogi das Cruzes – SP, Brazil; 32, Departamento de Gene´tica e Evoluc¸a˜o, Instituto de Biologia, Universidade Estadual de Campinas, Caixa Postal 6010,13083-970, Campinas– SP, Brazil; 33, Departamento de Botaˆnica, Instituto de Biocieˆncias, Universidade de Sa˜o Paulo, Rua do Mata˜o, 277, 05508-900, Sa˜o Paulo - SP, Brazil; 34, Departamento de Parasitologia, Microbiologia e Imunologia, Faculdade de Medicina de Ribeira˜o Preto, Universidade de Sa˜o Paulo, Av. Bandeirantes, 3900,14049-900, Ribeira˜o Preto – SP, Brazil; 35, Departamento de Psiquiatria, Instituto de Psiquiatria, Faculdade de Medicina, Universidade de Sa˜o Paulo, Rua Dr. Ovı´ deo Pires de Campos s/n, Sala 4051 (3o. andar), 05403-010, Sa˜o Paulo – SP, Brazil. † Present addresses: Novartis Seeds LTDA, Av. Prof. Vicente Rao, 90, 04706-900, Sa˜o Paulo – SP, Brazil (J. A. Machado); Centro de Cieˆncias Agra´rias e Ambientais, Pontifı´cia Universidade Cato´lica do Parana´, BR-376, Km 14, Caixa Postal 129, 83010-500, Sa˜o Jose´ dos Pinhais – PR, Brazil (H. M. F. Madeira); Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraı´ba, Av. Shishimi Hifumi, 2911, 12244-000, Sa˜o Jose´ dos Campos – SP, Brazil (F. G. Nobrega).
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
© 2000 Macmillan Magazines Ltd
157
270001
1
260
140
261 263 262
139
987
988
851
714
553
557
558
992
1530
1531
1402
853
559 560 XfP1
XfP4
726
561
1406
1266
1126
994
727
1535
860
2134
1979 1980
1
1
2
2
2687 2688
3
1285
2552
1981
2554
4 5 6
2689
2553
2418
7
2690
2555
2691
2419
2273 2275 2274
2138 2139
1269
9
10
569
1002
1133 1136 1134 1135
1001
2694 2695
2557
1988 1989
1851
1278
1137
12
1003
1990 1991
2696
2697 2698
2558
2426
2427
2285 2284
2428
2286
2699
2700
2559 2561 2562 2560
2283
1279
13
14
15
16
1855
1995
1856
17
1550
18
2701 2703 2702
1425
2571
2432
422
879
1427
1288
1724 1725 1726
2000 2002 2004 2001 2003
592
882
752
35
425
883
754
593
753
424
288 289
165
34
1727
1553
428
167
1554
1728
41
169
40
429
291
168
37 38 39
757
1025
886
26 27 29 30 28
2707 2708
2435 2436 2437
32 33 34 35
2709
36
2438
2575 2576 2577 2578
31
2434
2579
2302
1298
1730 1732 1731
37
38 39
2710
R 2581
44
294
1027 1028
1443
1735 1736 1737
40
2583
41
42
43
2311
44
1030
LR-7
1448 1449
2023
2024
2025
1889 1890
45 46
2714
2590
2448
47
48
2592
2450
49 50 51 52 53
2717 2720 2718 2719
2591
2449
tmRNA 2715 2716
2446 2447
54
55
2721
2593
2451
1749
1584 1586 1585
1452
890
1897
2722
59
60
2723
2596
61
2724
2597
62
1314
1182
2328
63
REPEAT-1
2598
64
2599
1455
1183
896
63
1187
1461
1462
621
51158
2725
2041 2042
2196
LR-7
2043
1904
2726
2602
2728
2605 2604
2727
2603
1763
2340
1 kb
1190 V D
1047
904 905
2608
2053
1914
1768
1609
2734
1474
2349
2206
472
796
1476
1477
1774 1775
2208
2060
2209
75
204
76 77
473
2061
1062
920
476 477
799
801
1063 1064
921 922 923
800
1924
2483 2485 2484
2742 2743 2745 2746 2744
2624
2486
2358
1927
2360
2361
1624 1625
A
2625
1931
2219
2628
2220
2629
928
1213
Frameshift/Point mutation (FSPM) Intron tRNA (letter indicates amino acid)
347
8485
212
86
87
348 351 349 350
213 214
929
1487
1351 1352
2498
1488
1353
810
933
657
88
352
215216 217 A
89
2083
2224
1078
1633 1634 1637 1635 1636
2500
2084
356
1223
820
1363
1497
1641
1499
1949
2385
2235
2092
2640 T Y G
2774
2641 26422643
824
106
825
673
232
368
M
107 109 110 108
1501
1502 1503
1372
1231
2236
2093
1807
2386
2647
2775
LR-7
2524
2237
953
826
955
827
954
674
676 677V
2238
1232
833
680
1234 K
1508
1106
963 964
834
681 682
118
965
966
835
683
523
1380
1381
374
1241
1382
1953
1814
2241 2242
2100
2526 2527
2776 2777
2651
2396
2244
2532 2533 2534
2397
2246 2247 2245
838
839
2250
2252 2253 2254
2111 2113 2112 2114
1962 1964 1963
1822
2251
1961
2536 2537
2538
378 380 379
2778
2779
2780
2781 2782
381
532 534 533 XfP1
1111
974
1112
975
841
1517
1384
1518
LR-3
382
535 536
2115
537
383
2677
2544
1386 1388 1387
1114
844
385 386 387
1389
1115
2258
2678
2545
1829
1830
2546
2408
2121
2679
2259
979 980
1527
1831 1832
2680
2547
2260
2548
2681
2549
1688
1528
1976
2550
2411
1529
391 392
1977
2551
2412 2413
2685
1692
1080000
945000
810000
675000
1215000
1350000
1755000
1890000
2025000
2687
2565000
2430000
2295000
2160000
2134
2552
2414
1485000
1620000
1979
2268
2686
2133
2267
405000
540000
1398
1258 1259
1978
135000
270000
L 1119 1120
985 986
848
712 713
550
1836 1837 1838
1689 1691 1690
1835
2262 2265 2266 2263 2264
2682 2683 2684
2409 2410
2261
1118
847
711
134
256 257 258
1392 1393 1394 1397 1395 1396
2122 2123 2125 2127 2128 2131 2124 2126 2129 2132 2130
1975
1833
984
390
255
1254 1255 1257 1256
1117
1834
1391
1253
710
549
982 981 983
846
707 709 708
1116
1390
706
1680 1681 1682 1683 1685 1687 1684 1686
978
845
133
254
388 389
253
132
540 542 544 546 548 541 543 545 547
1252
705
539
384
252
128 129 131 130
1969 1970 19711972 1973 1974
2120
1828
1967 1968
LR-6LR-6
2407
538
977
843
1676 1677 1679 1678
1827 1826
2116 2118 2117 2119
1966
1824 1825
2256 2257
2542 2543 2539 2540 2541
2255
1965
1823
1385
1250 1251
1113
976
842
127
244 245 247 249 250 251 246 248
125 126 S
1519 1521 1523 1524 1525 1526 1520 1522 REPEAT-IN-XfP3-AND-XfP4 XfP4
1245 1247 1248 1246 1249
973
840
1670 1672 1674 1675 1669 1671 1673
1244
1666 16671668
1516
1383
1242 1243
1110
2398 2399 2400 2402 2404 2406 2401 2405 2403
2249
377
527 528 529 530 531
243
124
686 687 689 691 693 695 696 697 699 701 703 704 688 692 694 698 700 702 690
LR-5
1108 1109
1821
2107C 2108 2110 2109
2535
2248
1960
1819 1820
123
2652 2655 2657 2659 2660 2662 2663 2664 2676 2666 2668 2670 2671 2672 2674 2653 2656 2658 2661 2667 2669 2673 2675 2665 2654 2679305
2528 2529 2530
1959
1818
2101 2103 2105 2106 2102 2104
2531
2243
1958
1815 1817 1816
1954 1956 1957 1955
2099
1813
122
240 241 242
972 V 968 969 970 971
685
526
376
120 121
239
375
837
684
967
1107
836
524 525
1509 1510 1511 1513 1514 1512 1515
1379
119
236 237 238
1235 1237 1239 1236 1238 1240
1104 1105
1376 1378 1377
1233
1103
2390 2392 2393 2395 2391 2394
2239 2240
1507
1375
679
522
373
235
116 117
1648 1649 1650 1653 1655 1656 1658 1659 1661 1663 1664 1665 1651 1654 1657 1660 1652 1662
2095 2096 2097 2098
1812
1647
2649 2650
2525
1373 1374
832
678
521
370 371 372
957 959 960 961 962 958
830 831 829
956
828
675
1504 1505 1506
2387 2389 2388
2648
2094
1952
1809 1811 1808 1810
1642 1643 1645 1646 1644
1500
2644 Q 2645 2646
1230
369
234
111 112 114 115 113
233
512 513 515 516 518 519 514 517 520
367
230 231
951 952
511
366
671 672
1369 1370 1371
1229
LR-5
1950 1951
1804 1805 S 1806
1498
823
670
510
947 948 949 950
509
105
228 229
104
1088 1090 1091 1093 1094 1096 1097 1098 1100 1102 1089 1092 1095 1099 1101
946
822
669
227
362 363 364 365
E
103
1364 1365 1366 1368 1367
2233 2234
2091
1948
2384
1947
1803
1087
945
821
508
1225 1227 1228 1226
944
226
359 361 360
225
100 101 102
507
358
224
2507 2510 2511 2512 2514 2516 2518 2521 2522 2523 2508 2513 2515 2517 2519 2509 2520 2636 2638 W 2637 2639
2506
2376 2379 2381 2383 2377 2380 2378 2382
2232
2090
1946
943
819
LR-4
506
1640
1800 1802 1801
1496
2763 2765 2767 27692770 2772 2764 2766 2768 2771 2773
2634 2635
2505
2375
2231
1945
2089
1944
1639
1799
1224
1362
99
223
1085 1084 1086 LR-1
942
1082 1083
941
818
668
357
505
222
94 95 96 97 98
817
1361
1494 1495
1360
1081
940
20872088
2760 P HK 2761 2762 R
2633
2501 2502 2504 2503
939
816
1798
1638
1797
2086
355
2226 2227 2229 2230 2228
2085
93
221
664 665 667 666
1079 1080
1221 1222
2370 2371 2372 2373 2374 XfP2
2225
663
1357 1358 1359
1220
354
92
497 499 501 503 504 498 500 502
936 937 938
1937 1938 1940 1942 1943 1939 1941
2367 2368 2369
2223
2759
2632
2499
2366
2222
91
220
814 813 815
178517861787 1788 1790 1792 1796 T 1794 1795 1789 1793 1791 1936
496
353
1489 1490 1491 1493 1492
1354 1355 1356
90
218 219
660 661 662
811 812
659
934 935
658
1077
1217 1219 1218
1075 1076 1074
1214 1216 1215
1073
930 932 931
807 809 808
656
1628 1629 1630 1631 1632
1486
1350
655
806
1072
654
1934 1935
2365
2221
2630 2631
2497
2362 2363 2364
2218
2747 2748 2750 2752 2753 2754 2756 2758 2749 2751 2755 2757
2626 2627
805
652 653
2069 2070 2073 2075 2077 2079 2081 2082 2071 2074 2076 2078 2080 2072
1932 1933
83
211
480 481 483 485 486 487 488 490 492 494 482 484 489 491 493 495
1626 1627
1485
1348 1349
82
343 344 346 345
210
1068 1069 1071 1070
927
1211 1212
1484
1210
926
803 804
651
479 N
342 341
209
81
1781 1782 1783 1784
1928 1930 1929
1777 1779 1778 1780
1623
1480 1482 1483 1481
1622
925
1347
2487 2488 2490 2492 2494 2496 2489 2491 2493 2495
2359
802
340
1065 1066 1067
924
1345 1346
2062 2064 2066 2068 2063 2065 2067
1925 1926
1776
1621
1479
1339 1341 1344 1340 1342 1343
1620
80
205 206 207 208
79
478
339
78
647 648 650 S 642 644 645 646 643 649
475
641
798
474
2211 2213 2214 2215 2216 2217 2210 2212
Transport Mobile genetic elements Pathogenicity and adaptation Conserved hypothetical Hypothetical
2741
74
1200 1201 1202 1204 1206 1209 1203 1205 1207 1208
1478
1338
1197 1198 1199
1615 1617 1618 1616 1619
1475
2618 2619 2620 2623 2621 2622
2482
2740
919
797
2350 2352 2354 2355 2357 2351 2353 2356
2207
2059
203
73
635 636 638 640 637 639
471
914 915 917 916 918
795
634
470
1917 1919 1920 1921 1923 1918 1922
2479 2480 2481
2739
1196
1772 1773 1771
202
324 325 326 327 328 330 332 335 338 331 333 336 329 334 337
LR-3
72
201
1056 1058 1060 A 1061 1055 1057 1059 L E
1611 1612 1614 1613
1770
1916
2617
1054
71
197 198 199 200
13311332 1333 1334 1335 1337 1336
2054 2057 2055 2058 2056
Macromolecule metabolism DNA processing RNA processing Cell structure Undefined category Cellular processes
2735 2736 2737 2738
1053
910
794
633
911 912 913
632
793
323
466 467 469 468
322
1471 1473 1472
1915
2477 2478
rRNA-operon
1192 1193 1195 1194
1769
2344 2346 2348 2345 2347
2475 2476
2343
A I
193 195 196 194
631
465
321
909
1610
1470
1330
2609 2610 2611 2613 2614 2615 2616 2612
2473 2474
2341 2342
908
2201 2202 2204 2205 2203
2050 2051 2052
907
1469
1766 1767
1911 1912 1913
1765
1606 1607 1608
1468
1191
1048
906
792
629 630
464
790 791
628
463
320
192
1049 1050 1052 1051
627
462
319
190 191
786 788 787 789
624 625 626
2197 2199 2198 2200
2049
1910
70
460 461
1327 1329 1328
903
1605
Intermediary metabolism Energy metabolism Regulatory functions Biosynthesis of small molecules Amino acid biosynthesis Nucleotide biosynthesis
2733
2607
623
785
459
189
318
1465 1466 1467
2472
2046 2047 2048
2467 2469 2470 2471 2468
2339
2044 2045
2729 2731 2730 2732
2606
2466
1761 1762
1764
1464
1906 1907 1908 1905 1909
2331 2332 2333 2334 2336 2338 2335 2337
2040
2461 2463 2465 2462 2464
2600 2601
2460
2330
2038 2039
1903
1754 1755 1757 1759 1756 1758 1760
1898 1899 1900 1901 1902
1753
1189
1046
317
187 188
69
68 R
458
901 902
622
186
67
1324 1325 1326
1463
1188
1319 1321 1322 1323 1320
316
782 783 784
456 457
315
620
900
66
184 185
65
1043 1045 1044
1186
1042
G
898 899
781
455
616 618 617 619
779 780
897
183
64
312 313 314
181 182
453 454
62
1458 1459 1460
1317 1318
L
1039 1041 1040
895
61
615
452
311
180
778
1184 1185
1456 1457
1316
179
451
1038
892 893 894
614
450
310
178
58 60 59
1588 1590 1592 1594 1596 1598 1600 1601 1602 1603 1604 1589 1591 1593 1595 1597 1599
2037
2329
613
777
1315
L
1037
891
2193 2195 2194
2454 2455 2456 2457 2459 2458
2327
2186 2188 2190 2192 2187 2189 2191
2326
2595
2453
56 57 58
REPEAT-1
2594
2452
2325
2185
612
776
1750 1751 1752
1587
1453
1313
309
177
54 56 55 57
308
176
53
446 447 449 448
1454
611
445
1181
1036
1892 1893 1894 1895 1896
1746 1747 1748
1583
1451
1312
1180
1032 1035 1033 1034
1310 1311
XfP3
610
442 444 443
609
175
52
307 L 305 304 306
174
51
769 770 772 773 775 771 774
608
440 441
303
50
2027 2028 2030 2032 2034 2035 2029 2031 2033 2026 2036
1891
1743 1744 1745
173
298 299 300 302 301
1575 1576 1577 1578 1580 1582 1579 1581
1742
2177 2178 2179 2181 2183 2184 2180 2182
2022
1888
1741
1450
49
172
1178 1179
1308 1309
REPEAT-IN-XfP3-AND-XfP4
1447
1305 1306 1307
1031
889
768
439
297
47 48
767 766
604 606 607 605
438
171
46
1173 1175 1176 1177 1174
1029
1571 1572 1574 1573
1740
603
437
296
170
762 763 764 765
602
436
295
45
2312 2313 2314 2316 2318 2320 2322 2324 2315 2317 2319 2321 2323
2176
2586 2587 2588 2589
2445
2713
2584 2585
2444
2307 2308 2309 G 2310
2170 2171 2173 2174 2175 2172
1887
1739
2020 2021
1738
1444 1446 1445
1304
761
600 601
888
760
435
rRNA-operon
433 434
A I
1303
1561 1562 1564 1566 1568 1569 1570 1563 1565 1567
1733 1734
2013 2015 2016 2018 2019 2014 2017
2711 2712
2582
2443
2306
2169
2010 2012 2011
2166 2167 2168
2009
2441 2442 2440
2580
2439
LR-2
887
599
1299 1300 1301 1302
1435 1437 1438 1439 1440 14411442 1436
1555 1557 1559 1556 1560 1558 1729
2303 2305 2304
2165
2005 2006 2008 2007
293 F
43
431 432
1026
759
430
292
42
1151 1153 1155 1157 1159 1161 1163 1165 1167 1169 1171 1172 1152 1154 1156 1158 1160 1164 1166 1168 1170 1162
885
758
595 596 597 598
756
884
755
594
426 427
290
166
36
1012 1014 1015 1016 1018 1020 1022 1024 1013 1017 1019 1021 1023
880 881
591
423
287
1428 1429 1431 1434 1430 1433 1432
2296 2298 2300 2301 2297 2299
2573 2574
2433
2295
2706
33
162 164 163
LR-1
1289 1290 1291 1292 1294 12951296 1297 1293
2159 2160 2161 2164 S 2156 2157 2158 2162 2163
2572
590
749 751 750
589
286
1146 1148 1150 1147 1149
1011
878 LR-4
876 877
1551 1552
1426
1287
1145
875
588
748
285
161
32
1859 1860 1863 1865 1867 1869 1870 1871 1873 1875 1876 1877 1878 1881 1882 1885 1861 1864 1866 1868 1872 1874 1879 1883 1886 1862 1880 1884
1996 1998 1999 1997
24 25
2705
19 20 22 21 23
2704
1424
1286
1144
874
31
157 159 158 160
30
585 586 587
282 284 283
156
28 29
743 745 747 746 744 P
584
1719 1721 1723 1720 1722
1857 K 1858
2431
2563 2564 2567 2568 2570 2565 2569 2566
2430
1143
1282 1283 1284 1285
1718
873
742
281
420 421
1006 1008 1010 1007 1009
870 872 871
2151 2152 2154 2155 2153
1994
280
154 155
27
577 580 581 583 578 582 579
741
1141 1142
1549
1423
1281
1005
869
740 738 739
576
2288 2289 2290 2291 2293 2292 2294
1993
1548
1717 G
26
152 153
278 279
151
22 25 23 M 24
414 416 417 419 415 418
277
1140
1280
1004
737
413
150
868
1138 1139
736
2429
2287
2149
1992
2150
1716
1852 1853 1854
2142 2143 2144 2145 2146 2147 2148
1987
1850
1712 1713 1715 1714
Plasmid pXF1.3 Gene Map
11
276
149
18 20 21 19
570 572 573 575 571 574
412
148
864 865 866 867
Plasmid pXF51 Gene Map
REPEAT-2 REPEAT-2
8
568
411
275
731 733 734 735 732
1132
1000
863
567
409 410
1270 1272 1274 1276 1271 1273 1277 1275
1131
2277 2279 2280 2282 2278 2281
2141
1986
1849
1985
999
730
566
408
274
147
17
1411 1413 1414 1415 1416 1418 1419 1422 1410 1412 1417 1420 1421
2421 2422 2423 2425 2424
2692 2693
2556
2420
2276
2140
1984
1845 1847 1848 1846
1982 1983
1843 1844
2137
2272
1842
2135 2136
1841
2270 2271
1838 1840 1839
146
1536 1538 1539 1540 1542 1545 1546 1537 1541 1544 1547 1543
1409
1268
1127 1128 1129 1130
145
268 269 271 273 270 272
144
861 862
728 729
996 998 997
1407 1408
1267
995
407
562 563 565 564
855 856 857 858 859
1533 1534
1405
1532
1403 1404
1265
993
854 P
LR-2
267
143
402 404 405 406 403
266
142
1693 1696 1699 1700 1703 1704 1705 1706 1707 1708 1709 1711 1694 1697 1701 1710 R 1695 1698 1702
1529
1125
989 990 991
852
1260 1261 1263 1262 1264
1398 1399 1401 1400
1259
554 556 555
401
264 265
141
715 717 718 720 723 724 725 716 719 721 722
1120 1121 1122 1124 1123
986
848 849 850
713
550 551 552
2414 2416 2417 T 2415
1
2565001
2430001
2295001
259
138
392 M 393 394 396 397 398 400 395 399 Q
258
2268 2269
2160001
2025001
1890001
1755001
1620001
1485001
1350001
1215001
1080001
945001
810001
675001
540001
405001
134 136 135 137
16
3.58
15
2.44
11 12 13 14
2.96
10
2.58
9
6.13
8
2.65
7
4.41
6
3.72
135001
2.89
Main Chromosome Gene Map
1.38
5
0.83
4
0.79
3
41.87
2
10.95
1
4.92
© 2000 Macmillan Magazines Ltd 4.61
158 3.27
1
articles
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
NATURE | VOL 406 | 13 JULY 2000 | www.nature.com
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Aerobic respiration
XF0347 D-lactate dehydrogenase (dld1) XF1802 glycerol-3-phosphate dehydrogenase (gpsA) XF2266 glycerol-3-phosphate dehydrogenase (glpD) XF0310 NADH-ubiquinone oxidoreductase, NQO1 subunit (nuoF) XF0314 NADH-ubiquinone oxidoreductase, NQO10 subunit (nuoJ) XF0315 NADH-ubiquinone oxidoreductase, NQO11 subunit (nuoK) XF0316 NADH-ubiquinone oxidoreductase, NQO12 subunit (nuoL) XF0317 NADH-ubiquinone oxidoreductase, NQO13 subunit (nuoM) XF0318 NADH-ubiquinone oxidoreductase, NQO14 subunit (nuoN) XF0309 NADH-ubiquinone oxidoreductase, NQO2 subunit (nuoE) XF0311 NADH-ubiquinone oxidoreductase, NQO3 subunit (nuoG) XF0308 NADH-ubiquinone oxidoreductase, NQO4 subunit (nuoD) XF0307 NADH-ubiquinone oxidoreductase, NQO5 subunit (nuoC) XF0306 NADH-ubiquinone oxidoreductase, NQO6 subunit (nuoB) XF0305 NADH-ubiquinone oxidoreductase, NQO7 subunit (nuoA) XF0312 NADH-ubiquinone oxidoreductase, NQO8 subunit (nuoH) XF0313 NADH-ubiquinone oxidoreductase, NQO9 subunit (nuoI)
34% 45%
37% 71% 41% 35%
XF2395 acetylxylan esterase (axeA) XF1250 arginine deaminase (rocF) XF1472 benzene 1,2-dioxygenase, ferredoxin protein (bedB) XF0840 beta-galactosidase (bga) XF0439 beta-glucosidase (bglX) XF0846 beta-mannosidase precursor XF1234 carboxyphosphonoenolpyruvate phosphonomutase (prpB) XF2210 dioxygenase XF1743 esterase (est) XF1610 fructokinase XF1740 glucose dehydrogenase B (yliI) XF1064 glucose kinase (glk) XF1460 glucose kinase (glk) XF1965 haloalkane dehalogenase (dhaA) XF2677 L-ascorbate oxidase (aao) XF1253 lipase (lipP) XF0781 lipase/esterase (estA) XF1825 NAD(P)H steroid dehydrogenase (cdh) XF1201 phosphoglycolate phosphatase (yfbT) XF2470 phosphoglycolate phosphatase (cbbZC) XF2259 polyvinylalcohol dehydrogenase XF0366 ribokinase (rbsK) XF0379 rubredoxin (rubA) XF1819 threonine dehydratase catabolic (tdcB) XF1181 triacylglycerol lipase precursor (lip) XF0610 UDP-glucose 4-epimerase (galE) XF2432 UTP-glucose-1-phosphate uridylyltransferase (gtaB)
XF1746 alcohol dehydrogenase (yahK) XF2389 alcohol dehydrogenase (yahK) XF1136 NADP-alcohol dehydrogenase XF1727 NADP-alcohol dehydrogenase (adh) XF1734 NADP-alcohol dehydrogenase
39%
41% 58%
57% 64%
76% 57% 63%
65% 54%
32% 55% 42% 33%
© 2000 Macm an Magaz nes L d
acetyl coenzyme A synthetase (acs) adenosylhomocysteinase (ahcY) carbonic anhydrase (yadF) carbonic anhydrase deoxyxylulose-5-phosphate synthase (dxs) ferredoxin-NADP reductase (fpr) glycerol kinase (glpK) glycine cleavage H protein (gcvH) glycine cleavage T protein (gcvT) glycine decarboxylase (gcvP) hydroxyacylglutathione hydrolase (gloB) inorganic pyrophosphatase (ppa) lactoylglutathione lyase (gloA) methionine adenosyltransferase (metK) tropinone reductase
61% 65% 46% 32% 55% 59% 59% 48% 55% 57% 45% 59% 63% 70% 43%
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/TCA cycle
XF0292 aconitate hydratase 2 (acnB)
40%
52%
72%
XF0869 dihydrolipoamide acetyltranferase (pdhB) 52% XF0868 dihydrolipoamide dehydrogenase (lpdA/lpd) 57% XF0669 pyruvate dehydrogenase (aceE) 56%
57% 55% 67%
XF1497 3’-phosphoadenosine 5’-phosphosulfate reductase (cysH) XF1501 ATP sulfurylase, large subunit (nodQ) XF1500 ATP sulfurylase, small subunit (cysD) XF1499 NADPH-sulfite reductase, flavoprotein subunit (cysJ) XF1498 NADPH-sulfite reductase, iron-sulfur protein (cysI)
XF1063 6-phosphogluconolactonase (pgl) 35% XF1065 glucose-6-phosphate 1-dehydrogenase (zwf) 46%
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Pyruvate dehydrogenase
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Oxidative branch, pentose pathway
84% 55%
68% 60% 56% 50% 48%
31% 63% 52% 79%
52%
48%
56%
46% 49% 56% 47% 70% 54% 40% 31% 30%
54%
51%
41%
63%
56%
69%
39% 34% 41%
32%
52% 39% 52%
84% 63%
50% 51%
XF0274 6-phosphofructokinase (pfkA) XF1291 enolase (eno) XF0826 fructose-bisphosphate aldolase XF0232 glucose-6-phosphate isomerase (pgi) XF0457 glyceraldehyde-3-phosphate dehydrogenase (gapA) XF0823 phosphoglycerate kinase (pgk) XF1893 phosphoglyceromutase (gpmA/gpm) XF0824 pyruvate kinase type II (pykA) XF0303 triosephosphate isomerase (tpiA/tpi)
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Glycolysis
XF2460 c-type cytochrome biogenesis membrane protein (cycK) XF2459 c-type cytochrome biogenesis protein (cycJ) XF2462 c-type cytochrome biogenesis protein (cycL) XF0620 c-type cytochrome biogenesis protein (copper tolerance) (dsbD) XF2461 c-type cytochrome biogenesis protein/thioredoxin (dsbE/ccmG) XF1328 cytochrome B561 (yodB) XF1360 cytochrome C oxidase assembly factor (coxD) XF1389 cytochrome O ubiquinol oxidase, subunit I (cyoB) XF1390 cytochrome O ubiquinol oxidase, subunit II (cyoA) XF1388 cytochrome O ubiquinol oxidase, subunit III (cyoC) XF1387 cytochrome O ubiquinol oxidase, subunit IV (cyoD) XF0253 electron transfer flavoprotein alpha subunit (etfA) XF0254 electron transfer flavoprotein beta subunit (etfB/etfS) XF1298 electron transfer flavoprotein ubiquinone oxidoreductase (etf-QO) XF0557 electron transfer protein azurin I (az1) XF0983 ferredoxin XF1964 ferredoxin (ykgJ) XF2601 ferredoxin XF0547 ferredoxin II (ydgM) XF0053 flavohemoprotein (fhp) XF2082 oxidoreductase XF1990 thioredoxin (yneN) XF0909 ubiquinol cytochrome C oxidoreductase, cytochrome B subunit (petB) XF0910 ubiquinol cytochrome C oxidoreductase, cytochrome C1 subunit (petC) XF0908 ubiquinol cytochrome C oxidoreductase, iron-sulfur subunit (petA)
81% 78% 56% 42% 56%
60%
56%
53%
87%
63%
58%
38%
41%
43%
50%
42%
69%
45%
53%
54%
46%
38%
45%
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Sulfur metabolism
XF0609 GDP-mannose 4,6 dehydratase (gmd) XF2279 nucleotide sugar epimerase (wbnF) XF0260 phosphoglucomutase/ phosphomannomutase (xanA) XF1468 phosphomannomutase (mrsA) XF0259 phosphomannose isomerase-GDPmannose pyrophosphorylase (xanB) XF1606 UDP-glucose dehydrogenase (ugd)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Sugar-nucleotide biosynthesis, conversions
XF2255 XF1037 XF0880 XF2095 XF2249 XF1889 XF2268 XF0181 XF0183 XF1385 XF2160 XF2171 XF1399 XF0392 XF0913
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Pool, multipurpose conversions
XF0657 alkaline phosphatase (phoA) XF0904 ATP-binding protein (ybeZ) XF2590 exopolyphosphatase (ppx) XF2591 polyphosphate kinase (ppk)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Phosphorus compounds
XF1288 CTP synthetase (pyrG) XF1058 uridylate kinase (pyrH)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Nucleotide interconversions
XF0208 D-ribulose-5-phosphate 3-epimerase (rpe/dod) XF2015 ribose-5-phosphate isomerase A (rpiA) XF1936 transketolase 1 (tktA/tkt)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Non-oxidative branch, pentose pathway
XF0977 malate oxidoreductase (maeB) XF1259 phosphoenolpyruvate synthase (ppsA/pps)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Gluconeogenesis
XF1061 2-keto-3-deoxy-6-phosphogluconate aldolase (eda/hga/kdgA) XF1062 6-phosphogluconate dehydratase (edd)
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Electron transport
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/Anaerobic respiration and fermentation
47% 45%
54%
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Entner-Douderoff
XF0141 glucosamine--fructose-6-phosphate aminotransferase (glmS) XF1464 glucosamine--fructose-6phosphateaminotransferase XF2355 N-acetyl-beta-glucosaminidase (exo) XF1465 N-acetylglucosamine-6-phosphate deacetylase (nagA)
INTERMEDIARY METABOLISM/CENTRAL INTERMEDIARY METABOLISM/Amino sugars
82%
62% 48% 46% 36% 44% 41% 35% 30% 29% 46% 25% 35% 35% 37% 22% 38% 54% 39% 56% 27%
XF0187 sulfite synthesis pathway protein (cysQ/amtA)
INTERMEDIARY METABOLISM/ DEGRADATION/Degradation of small molecules
ATP synthase, A chain (atpB/uncB/papD) ATP synthase, alpha chain (atpA/uncA) ATP synthase, B chain (atpF/uncF) ATP synthase, beta chain (atpD) ATP synthase, C chain (atpE/uncE) ATP synthase, delta chain (atpH/uncH) ATP synthase, epsilon chain (atpC) ATP synthase, gamma chain (atpG/uncG/papC)
57%
46% 74% 45% 78% 56% 37% 46%
36%
XF1241 aconitate hydratase 1 (acnA/acn) ---% XF1316 ATP:GTP 3’-pyrophosphotranferase (relA) 42% XF0125 carbon storage regulator (csrA) 84% XF2352 cold shock protein (scoF) 69% XF2476 extragenic supressor (suhB/ssyA) 44% XF2342 heat-inducible transcriptional repressor (hrcA) 40% XF0122 LexA repressor (lexA) 76% XF1182 lipase modulator (act) 53% XF1813 methanol dehydrogenase regulatory protein 53% XF1830 nitrile hydratase activator 46% XF1843 nitrogen regulatory protein P-II (glnB) 87% XF0352 pentaphosphate guanosine-3’pyrophosphohydrolase (spoT) 47% XF2145 phosphate regulon transcriptional regulator (phoU) 43% XF1275 poly(hydroxyalcanoate) granule associated protein (phaF) 20% XF2691 RNA polymerase sigma-32 factor (rpoH) 80% XF1408 RNA polymerase sigma-54 factor (rpoN) 64% XF1350 RNA polymerase sigma-70 factor (rpoD) 63% XF2239 RNA polymerase sigma-H factor (algU/algT) 56% XF1407 sigma-54 modulation protein 44% XF0911 stringent starvation protein A (sspA/ssp/pog) 46% XF0912 stringent starvation protein B (sspB) 42% XF2165 transcription-related protein (tex) 59% XF0962 transcriptional regulator (gcvR) 26% XF1749 transcriptional regulator (opdE) 77% XF1858 transcriptional regulator (exsB) 49% XF2038 transcriptional regulator (paiB) 31% XF2228 transcriptional regulator (algH) 45% XF2085 transcriptional regulator (AcrR family) 23% XF1254 transcriptional regulator (AraC family) (araL) 34% XF0767 transcriptional regulator (ArsR family) (hlyU) 34% XF1540 transcriptional regulator (Crp/Fnr family) (clp) 85% XF0821 transcriptional regulator (Fur family) (zur) 38% XF2344 transcriptional regulator (Fur family) (fur) 85% XF1463 transcriptional regulator (LacI family) 32% XF0972 transcriptional regulator (LuxR/UhpA family) (agmR/glpR) 38% XF2608 transcriptional regulator (LuxR/UhpA family) (gacA) 44% XF0833 transcriptional regulator (LysR family) (cysB) 39% XF1132 transcriptional regulator (LysR family) (act) 33% XF1730 transcriptional regulator (LysR family) (yafC) 35% XF1752 transcriptional regulator (LysR family) 80% XF1768 transcriptional regulator (LysR family) (ycjZ) 45% XF0216 transcriptional regulator (MarR family) (prsX) 22% XF1354 transcriptional regulator (MarR family) (yybA) 28% XF1490 transcriptional regulator (MarR/EmrR family) 26% XF1996 transcriptional regulator (PbsX family) 35% XF0061 transcriptional repressor (korB) 28% XF2062 transcriptional repressor (korC) 69% XF1920 Trp operon transcriptional repressor (trpR) 36% XF1094 tryptophan repressor binding protein (wrbA) 39% XF1133 tryptophan repressor binding protein 33% XF1733 tryptophan repressor binding protein 31% XF1455 two-component system, hybrid sensor/regulatory protein 28% XF0322 two-component system, regulatory protein (tctD) 45% XF0389 two-component system, regulatory protein (popP/feuP/phoP) 54% XF0450 two-component system, regulatory protein (pilH) 50% XF1113 two-component system, regulatory protein 30% XF1626 two-component system, regulatory protein (algR) 47% XF1848 two-component system, regulatory protein (glnG/ntrC/glnT) 51% XF2336 two-component system, regulatory protein (colR) 51% XF2534 two-component system, regulatory protein (colR) 59% XF2545 two-component system, regulatory protein (pilR) 58% XF2578 two-component system, regulatory protein (actR) 40% XF2593 two-component system, regulatory protein (phoB) 56% XF0323 two-component system, sensor protein (tctE) 31% XF0390 two-component system, sensor protein (phoQ)36%
acetylglutamate kinase (argB) acetylornithine deacetylase (argE) argininosuccinate lyase (asl) argininosuccinate synthase (argG) gamma-glutamyl phosphate reductase (proA) glutamate 5-kinase glutamate synthase, alpha subunit (gltB/aspB) glutamate synthase, beta subunit (gltD/aspB) glutamine synthetase (glnA) N-acetyl-gamma-glutamyl-phosphate reductase ornithine carbamoyltransferase (argF) pyrroline-5-carboxylate reductase (proC) succinylornithine aminotransferase (argM/astC/cstC)
XF2226 aspartate carbamoyltransferase (pyrB) XF1107 carbamoyl-phosphate synthase large chain (carB/pyrA) XF1106 carbamoyl-phosphate synthase small chain (carA) XF2439 cytidylate kinase (cmkA) XF0988 dihydroorotase (pyrC) XF2571 dihydroorotate dehydrogenase (pyrD) XF0153 orotate phosphoribosyl transferase (pyrE) XF0034 orotidine 5’-phosphate decarboxylase (pyrF)
37%
52% 38%
55% 57% 45% 34% 73% 42% 50% 33% 30% 34% 59%
33%
40%
59% 28% 62%
56% 47% 45% 60%
56%
cystathionine beta-synthase (cysB) cysteine synthase cysteine synthase (cysK) D-3-phosphoglycerate dehydrogenase (serA) phosphoserine aminotransferase (serC) serine hydroxymethyltransferase (glyA)
31% 27% 51% 62% 49% 71%
XF2216 amidotransferase (hisH) 43% XF2220 ATP phosphoribosyltransferase (hisG) 43% XF2214 cyclase (hisF) 61% XF2219 histidinol dehydrogenase (hisD) 50% XF2218 histidinol-phosphate aminotransferase (hisC) 42% XF2217 imidazoleglycerolphosphate dehydratase/histidinol-phosphate phosphatase bifunctional enzyme (hisB) 50%
BIOSYNTHESIS OF SMALL MOLECULES/AMINO ACIDS BIOSYNTHESIS/Histidine
XF1334 3-dehydroquinate synthase (aroB) 47% XF2324 3-phosphoshikimate 1-carboxyvinyltransferase (aroE) 46% XF0212 anthranilate phosphoribosyltransferase (trpD) 48% XF0210 anthranilate synthase component I (trpE) 57% XF0674 anthranilate synthase component I (trpE) 36% XF1914 anthranilate synthase component I (trpE) 37% XF0211 anthranilate synthase component II (trpG) 67% XF1915 anthranilate synthase component II (trpG) 43% XF0036 aromatic-amino-acid aminotranferase (tyrB) 55% XF0047 catabolic dehydroquinase (aroQ) 65% XF1141 chorismate mutase 25% XF2338 chorismate mutase 29% XF1369 chorismate synthase (aroC) 62% XF0213 indole-3-glycerol phosphate synthase (trpC) 63% XF1374 N-(5’-phosphoribosyl) anthranilate isomerase (trpF) 43% XF2325 P-protein (aroQ/pheA) 75% XF0026 phospho-2-dehydro-3-deoxyheptonate aldolase (aroG) 61% XF0624 shikimate 5-dehydrogenase (aroE) 43% XF1335 shikimate kinase (aroK) 40% XF1376 tryptophan synthase alpha chain (trpA) 46% XF1375 tryptophan synthase beta chain (trpB) 65%
BIOSYNTHESIS OF SMALL MOLECULES/AMINO ACIDS BIOSYNTHESIS/Aromatic amino acid family
XF0603 XF0128 XF0831 XF2206 XF2326 XF0946
59%
34% 70% 39%
44%
65% 45%
68% 48% 30% 51% 51% 41%
68%
52%
50%
53%
66%
50%
60%
64% 68%
59% 68% 64% 37% 52%
43% 47% 57% 59% 61%
39% 45% 70%
27%
42% 44% 59% 47%
37% 38%
44% 52%
58% 43% 50% 52%
35%
50%
XF1270 lipoate biosynthesis protein B (lipB) XF1269 lipoic acid synthetase (lipA/lip)
55% 60%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Lipoate
XF0228 2-amino-4-hydroxy-6hydroxymethyldihydropteridine pyrophosphokinase (folK) XF1456 2-amino-4-hydroxy-6hydroxymethyldihydropteridine pyrophosphokinase (folK) XF2431 bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (folD) XF2331 dihydrofolate reductase type III XF0436 dihydroneopterin aldolase (folB) XF0091 dihydropteroate synthase (folP) XF1946 folylpolyglutamate synthase/dihydrofolate synthase (folC/dedC) XF1983 GTP cyclohydrolase I (folE)
BIOSYNTHESIS OF SMALL MOLECULES/ COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Folic acid
XF1357 8-amino-7-oxononanoate synthase (bioF) 42% XF0189 adenosylmethionine-8-amino-7-oxononanoate aminotransferase (bioA) 47% XF1356 biotin biosynthesis protein (bioH/bioB) 36% XF0064 biotin synthase (bioB) 60% XF2099 biotin synthesis protein (bioC) 36% XF0356 cytochrome P-450 hydroxylase 37% XF0377 cytochrome P450-like enzyme (bioI) 37% XF2477 dethiobiotin synthetase (bioD) 44%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Biotin
XF1297 gluconolactonase precursor XF0608 mannosyltransferase (mtfA)
BIOSYNTHESIS OF SMALL MOLECULES/SUGARS AND SUGAR NUCLEOTIDES BIOSYNTHESIS
XF2089 5’-nucleotidase XF2150 diadenosine tetraphosphatase (apaH) XF0150 dUTPase (dut/dnaS/sof) XF1831 formyltetrahydrofolate deformylase (purU) XF2354 hypoxanthine-guanine phosphoribosyltransferase (hpt) XF2599 phosphodiesterase-nucleotide pyrophosphatase precursor XF2353 purine nucleoside phosphorylase XF2332 thymidylate synthase (thyA)
BIOSYNTHESIS OF SMALL MOLECULES/NUCLEOTIDES BIOSYNTHESIS/Salvage of nucleosides and nucleotides
XF0762 deoxycytidine triphosphate deaminase (dcd) XF1441 phosphohydrolase (orfU1) XF1196 ribonucleoside-diphosphate reductase alpha chain (nrdA) XF1197 ribonucleoside-diphosphate reductase beta chain (nrdB) XF1448 thioredoxin reductase (trxB) XF0580 thymidylate kinase
BIOSYNTHESIS OF SMALL MOLECULES/NUCLEOTIDES BIOSYNTHESIS/2’-Deoxyribonucleotides
BIOSYNTHESIS OF SMALL MOLECULES/NUCLEOTIDES BIOSYNTHESIS/Pyrimidine ribonucleotides
79% 78%
63%
XF0587 5’-phosphoribosyl-5-aminoimidazole synthetase (purM/purG) XF0585 5’-phosphoribosylglycinamide transformylase (purN) XF0275 adenylate kinase (adk) XF1553 adenylosuccinate lyase (purB) XF0455 adenylosuccinate synthetase (purA) XF1949 amidophosphoribosyltransferase (purF) XF1975 bifunctional purine biosynthesis protein (purH) XF2429 glutamine amidotransferase (guaA) XF1976 glycinamide ribonucleotide synthetase (purD) XF0560 GMP synthase XF1503 guanylate kinase (gmk/spoR) XF2430 inosine-5’-monophosphate dehydrogenase (guaB) XF0458 nucleoside diphosphate kinase (ndk) XF2644 phosphoribosyl pyrophosphate synthetase (prsA/prs) XF2671 phosphoribosylaminoimidazole carboxylase, ATPase subunit (purK) XF2672 phosphoribosylaminoimidazole carboxylase, catalytic subunit (purE) XF0205 phosphoribosylaminoimidazolesuccinocarboxamide synthase (purC) XF1423 phosphoribosylformylglycinamidine synthetase (purL/purI)
BIOSYNTHESIS OF SMALL MOLECULES/NUCLEOTIDES BIOSYNTHESIS/Purine ribonucleotides
XF2213 phosphoribosyl-AMP cyclohydrolase/phosphoribosyl-ATP pyrophosphatase bifunctional enzyme (hisI/hisIE) 56% XF2215 phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (hisA) 44%
60% 47%
48%
33% 36% 49%
53% 55% 64%
30% 28% 35% 36% 51% 46%
BIOSYNTHESIS OF SMALL MOLECULES/AMINO ACIDS BIOSYNTHESIS/Glycine-serine family|sulfur metabolism
XF0114 2,3,4,5-tetrahydropyridine-2-carboxylate N-succinyltransferase (dapD) XF1818 2-isopropylmalate synthase (leuA) XF2375 3-isopropylmalate dehydratase large subunit (leuA) XF2374 3-isopropylmalate dehydratase small subunit (leuD) XF2372 3-isopropylmalate dehydrogenase (leuB) XF1121 5,10-methylenetetrahydrofolate reductase (metF) XF2272 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase (metE) XF1821 acetolactate synthase isozyme II, large subunit (ilvG) XF1473 aminotransferase (nifS) XF2396 aminotransferase (aspC) XF0118 asparagine synthase B (asnB) XF1371 aspartate-B-semialdehyde dehydrogenase (asd) XF2100 aspartyl/asparaginyl beta-hydroxylase (aspH) XF2443 beta-alanine synthetase XF2225 bifunctional aspartokinase/homoserine dehydrogenase I (thrA/thrA1/thrA2) XF1116 bifunctional diaminopimelate decarboxylase/aspartate kinase (lysA) XF1999 branched-chain amino acid aminotransferase (ilvE) XF0864 cystathionine gamma-synthase (metB) XF1481 diaminopimelate epimerase (dapF) XF1105 dihydrodipicolinate reductase (dapB) XF0099 dihydroxy-acid dehydratase (ilvD) XF0963 dihydroxydipicolinate synthase (dapA) XF2211 enolase-phosphatase (masA) XF2224 homoserine kinase (thrB) XF0863 homoserine O-acetyltransferase (met2) XF2465 homoserine O-acetyltransferase XF1822 ketol-acid reductoisomerase (ilvC) XF0116 succinyl-diaminopimelate desuccinylase (dapE) XF2223 threonine synthase (thrC)
BIOSYNTHESIS OF SMALL MOLECULES/AMINO ACIDS BIOSYNTHESIS/Aspartate family, pyruvate family
XF0998 XF2712 XF1427
XF2709 XF1842 XF1002
71% 58%
69%
XF1001 XF1000 XF1003 XF0999 XF1005 XF1004 XF2710
38%
two-component system, sensor protein (phs) 37% two-component system, sensor protein (flhS) 35% two-component system, sensor protein (algZ) 40% two-component system, sensor protein (ntrB) 37% two-component system, sensor protein (colS) 34% two-component system, sensor protein (pilS) 37% two-component system, sensor protein (actS) 25% two-component system, sensor protein (phoR)38%
BIOSYNTHESIS OF SMALL MOLECULES/AMINO ACIDS BIOSYNTHESIS/Glutamate family|nitrogen assimilation
XF0853 XF0973 XF1625 XF1849 XF2535 XF2546 XF2577 XF2592
70%
53% 58% 30% 49% 75% 62% 57% 54%
61% 58%
INTERMEDIARY METABOLISM/REGULATORY FUNCTIONS
XF1149 XF1145 XF1147 XF1143 XF1148 XF1146 XF1142 XF1144
INTERMEDIARY METABOLISM/ENERGY METABOLISM, CARBON/ATP-proton motive force interconversion
XF1535 citrate synthase (gltA) XF1548 dihydrolipoamide dehydrogenase (lpd) XF1549 dihydrolipoamide S-succinyltransferase (sucB) XF1554 fumarate hydratase (fumC) XF1855 fumarate hydratase (fumB) XF2596 isocitrate dehydrogenase (icd) XF2700 isocitrate dehydrogenase (icd) XF1211 malate dehydrogenase (mdh) XF0942 malate:quinone oxidoreductase (yojH) XF1550 oxoglutarate dehydrogenase (odhA) XF1073 succinate dehydrogenase iron-sulfur protein (sdhB) XF1072 succinate dehydrogenase, flavoprotein subunit (sdhA) XF1070 succinate dehydrogenase, membrane anchor subunit (sdhC) XF1071 succinate dehydrogenase, membrane anchor subunit (sdhD) XF2548 succinyl-CoA synthetase, alpha subunit (sucD) XF2547 succinyl-CoA synthetase, beta subunit (sucC)
53% 42%
49% 50% 52%
33% 57% 67% 44%
46% 45% 41%
gamma-glutamyltranspeptidase (ggt) glutamate-cysteine ligase precursor (gsh1) glutaredoxin (grxC) glutaredoxin-like protein glutathione synthetase (gshB/gsh-II) thioredoxin (trxA) thioredoxin (ybbN) thioredoxin (trxA/tsnC/fipA)
39% 57% 53% 54% 53% 34% 31% 49%
63% 65% 48% 80% 76% 52% 20% 45% 45% 54% 27%
32%
XF0193 6-pyruvoyl tetrahydrobiopterin synthase (ygcM) XF1457 pteridine reductase 1 (ptr1/ltdH) XF2604 pterin-4-alpha-carbinolamine dehydratase (phhB) 34%
63% 37%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Biopterin
XF1886 phosphoglycerate mutase (pgmA)
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Cobalamin
XF0017 coproporphyrinogen III oxidase, aerobic (hemF) XF2306 delta-aminolevulinic acid dehydratase (hemB) XF0566 ferrochelatase (hemH) XF2302 glutamate-1-semialdehyde 2,1-aminomutase (hemL) XF2648 glutamyl-tRNA reductase (hemA) XF1627 hydroxymethylbilane synthase (hemC) XF1797 porphyrin biosynthesis protein (hemY) XF1512 protoporphyrinogen oxidase (hemK) XF0832 siroheme synthase (cysG) XF1332 uroporphyrinogen decarboxylase (hemE) XF1799 uroporphyrinogen-III synthase (hemD)
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Heme, porphyrin
XF0835 2-octaprenyl-6-methoxyphenol hydroxylase (ubiH/visB) 34% XF2471 3-demethylubiquinone-9 3-methyltransferase (ubiG/pufX) 49% XF0661 geranyltranstransferase (farnesyl-diphosphate synthase) (ispA) 54% XF0068 hydroxybenzoate octaprenyltransferase (ubiA/cyr) 52% XF1391 octaprenyl-diphosphate synthase (ispB/cel) 49% XF1538 ubiquinone biosynthesis protein (coq7) 29% XF1833 ubiquinone biosynthesis protein (aarF) 43% XF1487 ubiquinone/menaquinone transferase (ubiE) 58%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Menaquinone, ubiquinone
XF0984 XF1428 XF2595 XF2394 XF1956 XF1199 XF2174 XF2698
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Thioredoxin, glutaredoxin, glutathione
XF1748 5-amino-6-(5-phosphoribosylamino)uracil reductase 21% XF0954 6,7-dimethyl-8-ribityllumazine synthase (ribH) 45% XF0953 GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase (ribA) 52% XF1992 riboflavin biosynthesis protein (ribA) 35% XF2419 riboflavin biosynthesis protein (ribF) 43% XF0952 riboflavin synthase alpha chain (ribE) 45% XF0950 riboflavin-specific deaminase (ribD/ribG) 51%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Riboflavin
XF1048 1-deoxy-D-xylulose 5-phosphate reductoisomerase (dxr) XF0621 phosphomethylpyrimidine kinase XF0378 thiamin-phosphate pyrophosphorylase (thiE) XF0594 thiamine biosynthesis lipoprotein ApbE precursor (apbE) XF0783 thiamine biosynthesis protein (thiG) XF1888 thiamine biosynthesis protein (thiC/thiA) XF0956 thiamine-monophosphate kinase (thiL)
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Thiamin
XF1924 L-aspartate oxidase 40% XF1961 NH3-dependent NAD synthetase (nadE/adgA) 47% XF1097 nicotinate phosphoribosyltransferase (pncB) 43% XF1925 nicotinate-mononucleotide pyrophosphorylase (nadC) 54% XF1923 quinolinate synthetase A (nadA) 42%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Pyridine nucleotides
XF0060 pyridoxal phosphate biosynthetic protein (pdxJ) XF0839 pyridoxal phosphate biosynthetic protein (pdxA) XF1337 pyridoxamine 5’-phosphate oxidase (fprA)
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Pyridoxine
XF0229 3-methyl-2-oxobutanoate hydroxymethyltransferase (panB) 55% XF0231 aspartate 1-decarboxylase precursor (panD) 53% XF0230 pantoate--beta-alanine ligase (panC) 46%
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Pantothenate
XF0466 molybdopterin biosynthesis protein (moeB) XF1545 molybdopterin biosynthesis protein
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Molybdopterin 25%
ATP-dependent DNA helicase (rep) ATP-dependent helicase (yoaA) ATP-dependent helicase chromosomal replication initiator (dnaA) DNA gyrase subunit A (gyrA) DNA gyrase subunit B (gyrB) DNA ligase (ligA/lig/dnaL/pdeC/lop) DNA polymerase I (polA/resA) DNA polymerase III holoenzyme chi subunit (holC) DNA polymerase III subunit (dnaX/dnaZ/dnaZX) DNA polymerase III, alpha chain (dnaE/polC) DNA polymerase III, beta chain (dnaN) DNA polymerase III, delta subunit (holB) DNA polymerase III, delta subunit (holA) DNA polymerase III, epsilon chain (dnaQ) DNA primase (dnaG/dnaP/parB) DNA primase (traC) DNA topoisomerase I (topA) DNA topoisomerase III (topB) DNA/pantothenate metabolism flavoprotein (dfp) glucose inhibited division protein (gidB) glucose inhibited division protein A (gidA) helicase, ATP dependent (hrpA) primosomal protein N’ (priA) replicative DNA helicase (dnaB/groP/grpA) TldD protein (tldD) topoisomerase IV subunit (parC) topoisomerase IV subunit B (parE)
chromosome segregation protein (smc) DNA-binding protein (bbh3) DNA-binding protein (fis) histone-like protein (hbs/hbsU) histone-like protein single-stranded DNA binding protein (ssb) single-stranded DNA binding protein (ssb) single-stranded DNA binding protein (ssb) single-stranded DNA binding protein (ssb) single-stranded DNA binding protein (ssb)
30% 29% 53% 73% 72% 54% 38% 91% 45% 53% 81%
53% 38%
32%
55% 54% 35%
27% 33% 58% 64% 54% 49% 56% 36% 54% 25%
51% 45% 65% 50% 44% 53% 61% 61% 64%
48% 51% 35% 29% 49% 46% 56% 41% 48%
40%
34%
43% 43% 43% 53% 57% 60% 46% 52%
66% 41%
XF2598 6-O-methylguanine-DNA methyltransferase (dat/dat1) 46% XF1262 7,8-dihydro-8-oxoguanine-triphosphatase (mutX) 38% XF1909 A/G-specific adenine glycosylase (mutY/mutB) 46% XF0050 DNA helicase II (uvrD/mutU/pdeB/rad/recL) 56%
MACROMOLECULE METABOLISM/DNA METABOLISM/Repair
XF0354 ATP-dependent DNA helicase (recG) XF1381 DNA helicase XF2248 DNA repair protein RecO (recO) XF0003 DNA replication and repair RecF protein (recF/uvrF) XF1892 endonuclease V (deoxyinosine 3’endonuclease) (nfi) XF0425 exodeoxyribonuclease V alpha chain (recD) XF0423 exodeoxyribonuclease V beta chain (recB/rorA) XF0422 exodeoxyribonuclease V gamma chain (recC) XF1425 integrase/recombinase (xerD/xprB) XF0743 integration host factor, alpha subunit (himA) XF2437 integration host factor, beta subunit (himD) XF1809 recombination protein (recR) XF2343 recombination protein N (recN) XF0123 recombination protein RecA (recA) XF1110 single-stranded DNA exonuclease (recJ) XF1483 site-specific recombinase (sss/xerC) XF2028 site-specific recombinase (rin)
MACROMOLECULE METABOLISM/DNA METABOLISM/Recombination
XF2558 XF0446 XF1998 XF1190 XF1943 XF0482 XF1392 XF1558 XF1644 XF1778
MACROMOLECULE METABOLISM/DNA METABOLISM/Structural DNA binding proteins
XF1935 XF2106 XF1383 XF2689 XF0361 XF1127 XF1353 XF1286
XF0002 XF0676 XF2178 XF2157 XF0430 XF2025 XF0920 XF1776 XF0149
XF0204
XF1807
XF2680 XF0882 XF1229 XF0001 XF2552 XF0005 XF2556 XF1103 XF0136
MACROMOLECULE METABOLISM/DNA METABOLISM/Replication
XF0144 biosynthetic arginine decarboxylase (speA) XF1539 S-adenosyl methionine decarboxylase proenzyme (speD) XF0143 spermidine synthase (speE)
45%
(3r)-hydroxymyristoyl ACP dehydrase (fabZ) 49% 3-alpha-hydroxysteroid dehydrogenase 34% 3-oxoacyl-[ACP] reductase 42% 3-oxoacyl-[ACP] reductase (fabG) 66% 3-oxoacyl-[ACP] synthase II (fabF) 60% 3-oxoacyl-[ACP] synthase III 24% acetoacetyl-CoA reductase (phbB) 65% acetyl-coenzyme A carboxylase carboxyl transferase subunit alpha (accA) 64% acetyl-coenzyme A carboxylase carboxyl transferase subunit beta (accD/dedB/usg) 62% acyl carrier protein (acpP) 72% acyl carrier protein (acpC) 40% beta-hydroxydecanoyl-ACP dehydratase (fabA) 63% beta-ketoacyl-[ACP] synthase II (fabF/fabJ) 34% beta-ketoacyl-[ACP] synthase III (fabH) 62% biotin carboxyl carrier protein of acetyl-CoA carboxilase (accB/fabE) 53% biotin carboxylase subunit of acetyl CoA carboxylase (accC/fabG) 76% cardiolipin synthase 33% cardiolipin synthase (cls/nov) 34% ketoreductase 29% malonyl CoA-ACP transacylase (fabD) 51% phosphatidate cytidylyltransferase (cdsA/cds) 36% phosphatidylserine decarboxylase (psd) 44%
BIOSYNTHESIS OF SMALL MOLECULES/POLYAMINES BIOSYNTHESIS
XF1087 XF1209 XF2716 XF0670 XF1049 XF1365
XF0049
XF1639 XF1817 XF0048
XF0672 XF0771 XF0572
XF1467
XF1044 XF2269 XF0173 XF0671 XF0673 XF1970 XF0319 XF0203
BIOSYNTHESIS OF SMALL MOLECULES/FATTY ACID AND PHOSPHATIDIC ACID BIOSYNTHESIS
XF1916 coenzyme F390 synthetase
BIOSYNTHESIS OF SMALL MOLECULES/COFACTORS, PROSTHETIC GROUPS, CARRIERS BIOSYNTHESIS/Others
adenine-specific methylase DNA methylase DNA methyltransferase (sfiIM) DNA methyltransferase (gene with intron) DNA processing chain A (smf/dprA) methyltransferase methyltransferase (kpnIM) site-specific DNA-methyltransferase (sphIM) site-specific DNA-methyltransferase type I restriction-modification system (hsdM) type I restriction-modification system DNA methylase type I restriction-modification system DNA methylase (hsdM) type I restriction-modification system DNA methylase type I restriction-modification system DNA methylase (hsdM) type I restriction-modification system endonuclease type I restriction-modification system endonuclease (hsdR1) type I restriction-modification system endonuclease type I restriction-modification system endonuclease (hsdR) type I restriction-modification system specificity determinant type I restriction-modification system specificity determinant type I restriction-modification system specificity determinant (hsdS) type I restriction-modification system specificity determinant (hsdS)
XF2438 XF1151 XF1174 XF2631 XF1173 XF1165 XF0238 XF0107 XF1161 XF2560 XF1156 XF2580 XF2421 XF0434 XF1158 XF1175 XF1169 XF2561 XF2630 XF1166 XF1536 XF2636 XF2635 XF2637 XF1537 XF1162 XF1171 XF1159 XF1177 XF1168 XF0110 XF1155 XF0740 XF2424 XF1157 XF1154 XF1163 XF2643 XF2423 XF1206 XF1160 XF1152 XF1170 XF1534 XF1816 XF1207 XF2782 XF0739 XF2440 XF1153 XF1164 XF1167 XF2634 XF2559
30S ribosomal protein S1 (rpsA/ssyF) 30S ribosomal protein S10 (rpsJ) 30S ribosomal protein S11 (rpsK) 30S ribosomal protein S12 (rpsL) 30S ribosomal protein S13 (rpsM) 30S ribosomal protein S14 (rpsN) 30S ribosomal protein S15 (rpsO/secC) 30S ribosomal protein S16 (rpsP) 30S ribosomal protein S17 (rpsQ) 30S ribosomal protein S18 (rpsR) 30S ribosomal protein S19 (rpsS) 30S ribosomal protein S2 (rpsB) 30S ribosomal protein S20 (rpsT) 30S ribosomal protein S21 (rpsU) 30S ribosomal protein S3 (rpsC) 30S ribosomal protein S4 (rpsD) 30S ribosomal protein S5 (rpsE/spc) 30S ribosomal protein S6 (rpsF) 30S ribosomal protein S7 (rpsG/rps7) 30S ribosomal protein S8 (rpsH/rps8) 30S ribosomal protein S9 (rpsI/rps9) 50S ribosomal protein L1 (rplA/rpl1) 50S ribosomal protein L10 (rplJ) 50S ribosomal protein L11 (rplK/relC) 50S ribosomal protein L13 (rplM) 50S ribosomal protein L14 (rplN) 50S ribosomal protein L15 (rplO) 50S ribosomal protein L16 (rplP) 50S ribosomal protein L17 (rplQ) 50S ribosomal protein L18 (rplR) 50S ribosomal protein L19 (rplS) 50S ribosomal protein L2 (rplB) 50S ribosomal protein L20 (rplT) 50S ribosomal protein L21 (rplU) 50S ribosomal protein L22 (rplV) 50S ribosomal protein L23 (rplW) 50S ribosomal protein L24 (rplX) 50S ribosomal protein L25 (rplY) 50S ribosomal protein L27 (rpmA) 50S ribosomal protein L28 (rpmB) 50S ribosomal protein L29 (rpmC) 50S ribosomal protein L3 (rplC/rpl3) 50S ribosomal protein L30 (rpmD) 50S ribosomal protein L31 (rpmE) 50S ribosomal protein L32 (rpmF) 50S ribosomal protein L33 (rpmG) 50S ribosomal protein L34 (rpmH) 50S ribosomal protein L35 (rpmI) 50S ribosomal protein L36 (rpmJ) 50S ribosomal protein L4 (rplD) 50S ribosomal protein L5 (rplE/rpl5) 50S ribosomal protein L6 (rplF) 50S ribosomal protein L7/L12 (rplL) 50S ribosomal protein L9 (rplI)
MACROMOLECULE METABOLISM/RNA METABOLISM/Ribosomal proteins
XF2741
XF2726
XF2722
XF0296
XF2739
XF2725
XF2721
XF0295
XF2742
XF2728
XF2723
XF1368 XF2297 XF0641 XF1774 XF0924 XF0935 XF1968 XF1804 XF2313 XF2724 XF0297
MACROMOLECULE METABOLISM/DNA METABOLISM/Restriction, modification
XF0760 DNA mismatch repair protein MutL (mutL) XF0148 DNA repair protein (radC) XF1378 DNA repair protein (radA/sms) XF1299 DNA repair system specific for alkylated DNA (alkB) XF1326 DNA-3-methyladenine glycosidase (mag1) XF1806 DNA-damage-inducible protein (dinD/pcsA) XF2081 DNA-damage-inducible protein (dinJ) XF0647 endonuclease III (nth) XF2426 excinuclease ABC subunit A (uvrA) XF0967 excinuclease ABC subunit B (uvrB) XF2311 excinuclease ABC subunit C (uvrC) XF0164 exodeoxyribonuclease XF2022 exodeoxyribonuclease I (sbcB/xonA/cpeA) XF1933 exodeoxyribonuclease II I (xthA) XF0660 exodeoxyribonuclease small subunit (xseB) XF0755 exodeoxyribonuclease VII large subunit (xseA) XF0071 formamidopyrimidine DNA glycosylase (mutM/fpg) XF0170 formamidopyrimidine DNA glycosylase (mutM/fpg) XF1902 holliday junction binding protein, DNA helicase (ruvB) XF1904 holliday junction binding protein, DNA helicase (ruvA) XF1905 holliday junction resolvase, endodeoxyribonuclease (ruvC) XF1716 mismatch repair protein (mutS) XF0045 transcription-repair coupling factor (mfd) XF2692 uracil-DNA glycosylase (ung)
67% 72% 86% 81% 85% 62% 62% 65% 51% 70% 60% 60% 54% 67% 67% 84% 71% 67% 60% 56% 68% 64% 43% 69% 71% 80% 48% 69% 80% 53% 65% 69% 72% 53% 63% 52% 48% 48% 64% 71% 50% 61% 47% 57% 75% 73% 76% 60% 65% 54% 63% 52% 67% 52%
24%
24%
21%
27%
42%
53%
20%
---%
53%
61%
44%
---%
46% 40% 31% ---% 37% 37% 33% 39% 41% 25%
52% 54% 49% 55%
42%
69%
51%
51%
41%
28% 35% ---% 57% 67% 70% 83% 50% 43% 43% 46% 39%
42% 41% 61%
alanyl-tRNA synthetase (alaS/lovB) 56% arginyl-tRNA synthetase (argS) 40% asparaginyl-tRNA synthetase (asnS/tss) 66% aspartyl-tRNA synthetase (aspS) 53% cysteinyl-tRNA synthetase (cysS) 46% glutaminyl-tRNA synthetase (glnS) 54% glutamyl-tRNA synthetase (gltX) 54% glycyl-tRNA synthetase alpha chain (glyQ/glyS(A)) 74% glycyl-tRNA synthetase beta chain (glyS/glyS(B)) 39% histidyl-tRNA synthetase (hisS) 36% isoleucyl-tRNA synthetase (ileS/ilvS) 54% leucyl-tRNA synthetase (leuS) 58% lysyl-tRNA synthetase (lysU) 56% lysyl-tRNA synthetase (yjeA/genX) 47% methionyl-tRNA formyltransferase (fmt) 56% methionyl-tRNA synthetase (metG) 54% phenylalanyl-tRNA sinthetase beta chain (pheT) 42% phenylalanyl-tRNA synthetase alpha chain (pheS) 59% prolyl-tRNA synthetase (proS/drpA) 55% ribonuclease D (rnd) 31% ribonuclease P (rnpA) 37% S-adenosylmethionine: tRNA ribosyltransferase-isomerase (queA) 52% seryl-tRNA synthetase (serS) 59% threonyl-tRNA synthetase (thrS) 59% tRNA (guanine-N1-)-methyltransferase (trmD) 51% tRNA adenylyltransferase (cca) 52% tRNA delta(2)-isopentenylpyrophosphate transferase (miaA/trpX) 49% tRNA methyltransferase (trmU/asuE) 55% tRNA pseudouridine synthase A (truA/hisT/asuC/leuK) 52% tRNA pseudouridine synthase B (truB) 42% tRNA/rRNA methyltransferase 41% tryptophanyl-tRNA synthetase 34% tyrosyl-tRNA synthetase (tyrS) 53% valyl-tRNA synthetase (valS) 51%
38% 38% 57% 50%
42% 35%
---%
46%
54%
36% 43% 53%
72% 62%
67% 71% 43% 60% 49%
52% 55% 52% 56% 48% 48% 87%
oligoribonuclease (orn) polynucleotide phosphorylase (pnp) ribonuclease ribonuclease H (rnhA/rnh) ribonuclease HII (rnhB) ribonuclease III (rnc) ribonuclease PH (rph) ribonuclease T (rnt)
XF1111 XF0174
XF0576 XF0111 XF2649
XF1445 XF0235 XF0737 XF0857 XF2417 XF2298
XF1018 XF1436 XF1834 XF2629 XF2203 XF2473 XF2579 XF2628 XF2640 XF2553
arginine-tRNA-protein transferase (ate1) disulfide oxidoreductase (dsbA) disulphide isomerase elongation factor G (fusA) elongation factor P (yeiP) elongation factor P (efp) elongation factor Ts (tsf) elongation factor Tu (tufA) elongation factor Tu (tufB) initiation factor eIF-2B, alpha subunit-related initiation factor IF-1 (infA) initiation factor IF-2 (infB) initiation factor IF-3 (infC) L-isoaspartate O-methyltransferase (pcm) lipoprotein signal peptidase (lspA) low molecular weight phosphotyrosine protein phosphatase (stp1) metallopeptidase methionine aminopeptidase (map) peptide chain release factor 1 (prfA/sueB/uar) peptide chain release factor 2 (prfB) peptide chain release factor 3 (prfC)
MACROMOLECULE METABOLISM/PROTEIN METABOLISM/Translation and modification
XF1257 XF0239 XF2615 XF2158 XF1041 XF2246 XF1505 XF2146
61% 66% 62%
40% 37% 60%
50% 73% 49% 60% 47% 45%
25% 38% 30% 70% 39% 63% 50% 82% 82%
58% 64% 44% 60% 55% 50% 63% 47%
MACROMOLECULE METABOLISM/RNA METABOLISM/RNA degradation
ATP-dependent RNA helicase (rhlE) ATP -dependent RNA helicase (deaD) ATP-dependent RNA helicase (rhlB/mmrA) N utilization substance protein A (nusA) polynucleotide adenyltransferase (pcnB) pseudouridylate synthase (rluC) RNA polymerase alpha subunit (rpoA) RNA polymerase beta subunit (rpoB/groN/nitB/rif/ron) XF2632 RNA polymerase beta’ subunit (rpoC/tabB) XF1502 RNA polymerase omega subunit (rpoZ) XF2638 transcription antitermination factor (nusG) XF0955 transcription termination factor (nusB/ssyB) XF2699 transcription termination factor Rho (rho/nitA/psuA/rnsC/tsu) XF1108 transcriptional elongation factor (greA)
XF0192 XF0252 XF2696 XF0234 XF0227 XF2606 XF1176 XF2633
MACROMOLECULE METABOLISM/RNA METABOLISM/RNA synthesis, modification, DNA transcription
XF0237 XF2475 XF0428 XF0169 XF0134
XF1440 XF1373
XF2286 XF0736 XF0109 XF1362 XF0090
XF0445 XF0751 XF2781 XF1314
XF0741
XF2222 XF2418 XF2176 XF1112 XF2555 XF0927 XF0549 XF0742
XF1959
XF0124 XF0147 XF2563 XF1856 XF0995 XF1338 XF0822 XF1960
MACROMOLECULE METABOLISM/RNA METABOLISM/Aminoacyl tRNA synthetases, tRNA modification
XF0108 16S rRNA processing protein (rimM) XF2607 ribonuclease E (rne/ams/hmp1) XF1125 ribonuclease G (cafA/rng) XF0939 ribosomal large subunit pseudouridine synthase D (rluD/sfhB) XF2201 ribosomal protein L11 methyltransferase (prmA) XF2532 ribosomal protein S6 modification protein (rimK) XF1200 ribosomal small subunit pseudouridine synthase (rsuA) XF0236 ribosomal-binding factor A (rbfA) XF0441 ribosomal-protein-alanine acetyltransferase (rimI) XF2358 RNA methyltransferase (ygcA) XF1972 tRNA/rRNA methylase (yibK) XF1985 tRNA/rRNA methyltransferase (yjfH)
MACROMOLECULE METABOLISM/RNA METABOLISM/Ribosomes - maturation and modification
10kDa chaperonin (groES/htpA) 60kDa chaperonin (mopA/groEL) chaperone (lolA) DnaJ protein (dnaJ) DnaJ protein (dnaJ) DnaK protein (dnaK/grpF/groP/seg) DnaK supressor heat shock protein G (htpG) heat shock protein GrpE (grpE) peptidyl-prolyl cis-trans isomerase (tig)
64% 41% 33% 28% 28% 65% 66% 33% 36% 34% 63% 50% 44% 53% 47% 33% 81% 22% 28% 27% 25% 39% 40%
61%
69%
73%
73%
30% 47% 36% 46%
59% 77% 32% 41% 59% 72% 48% 58% 38% 32%
34% 58% 40% 39% 54%
59% 49% 38% 43% 32% 25% 60% 36% 37% 55% 35% 51%
24% 31%
36%
XF2392 autolytic lysozyme (lyc) XF0847 beta-hexosaminidase precursor (nahA) XF2184 membrane-bound lytic transglycosylase (mltB)
CELL STRUCTURE/MEMBRANE COMPONENTS/Outer membrane constituents
XF2780 60kDa inner-membrane protein XF1640 ankyrin-like protein (ank2) XF2235 bifunctional penicillin-binding protein 1C precursor (pbpC) XF0082 chaperone protein precursor (ecpD) XF0851 D-amino acid dehydrogenase subunit (dadA/dadR) XF2334 diacylglycerol kinase (dgkA) XF0340 disulfide bond formation protein B (dsbB) XF2433 epimerase/dehydratase protein (capD) XF0256 glucose-1-phosphate thymidylyltransferase (rfbA) XF0375 inner membrane protein (yjdB) XF0103 membrane protein XF0764 membrane protein XF0777 membrane protein (actII-3) XF2230 penicillin-binding protein 6 precursor (dacC) XF0151 phosphomannomutase (algC) XF1183 polysaccharide biosynthetic protein (vipA/tviB) XF2333 prolipoprotein diacylglyceryl transferase (lgt/umpA) XF1310 rod shape-determining protein (mreC) XF1313 rod shape-determining protein (mrdB/rodA) XF1979 transmembrane protein (ampE) XF1140 UDP-N-acetylglucosamine pyrophosphorylase (glmU)
CELL STRUCTURE/MEMBRANE COMPONENTS/Inner membrane
XF2310 CDP-diacylglycerol-glycerol-3-phosphate 3phosphatidyltransferase (pgsA) XF1031 glycerol-3-phosphate acyltransferase (plsB)
36%
30% 37%
49%
48% 37% 48% 28%
52%
78% 36% 25% 36% 22% 47% 45%
54% 54% 33% 37%
47% 40%
40% 26%
49% 37%
MACROMOLECULE METABOLISM/OTHER MACROMOLECULES METABOLISM/Phospholipids
XF2714 alpha-L-fucosidase (fucA1) XF2278 dolichol-phosphate mannosyltransferase (dpm1) XF0887 mannosyltransferase (mtfA)
MACROMOLECULE METABOLISM/OTHER MACROMOLECULES METABOLISM/Polysaccharides
XF2260 alanyl dipeptidyl peptidase XF0138 aminopeptidase A/I (pepA/xerB/carP) XF1488 aminopeptidase N XF2009 aminopeptidase P (pepP) XF1188 ATP-dependent Clp protease ATP binding subunit Clpx (clpX/lopC) XF1187 ATP-dependent Clp protease proteolytic subunit (clpP/lopP) XF0381 ATP-dependent Clp protease subunit (clpB/htpM) XF1443 ATP-dependent Clp protease subunit (clpA/lopD) XF1189 ATP-dependent serine proteinase La (lon/capR/deg/muc/lopA) XF2704 carboxyl-terminal protease (ctpA) XF1282 carboxypeptidase related protein XF0156 cysteine protease (cpr6) XF0015 dipeptidyl-peptidase XF1484 heat shock protein (hslV/htpO) XF1485 heat shock protein (hslU/htpI) XF0452 integral membrane protease (hflK/hflA) XF0453 integral membrane proteinase (hflC) XF0280 leucine aminopeptidase (pepA) XF0435 O-sialoglycoprotein endopeptidase (gcp) XF0127 oligopeptidase A (prlC/opdA/optA) XF1479 peptidase (ptrB/tlp) XF1944 peptidyl-dipeptidase (dcp) XF2241 periplasmic protease (mucD) XF0220 proline dipeptidase (pepQ) XF1510 proline imino-peptidase (pip/xap) XF2330 proteinase (slpD) XF0267 serine protease (pspB) XF1026 serine protease (pspB) XF1851 serine protease XF1823 tail-specific protease (prc/tsp) XF0816 zinc protease
MACROMOLECULE METABOLISM/PROTEIN METABOLISM/Protein degradation
XF0616 XF0615 XF1452 XF2233 XF2339 XF2340 XF0991 XF0978 XF2341 XF1186
MACROMOLECULE METABOLISM/PROTEIN METABOLISM/Chaperones
XF1940 peptide methionine sulfoxide reductase (msrA/pms) XF2642 peptidyl tRNA hydrolase (pth) XF0644 peptidyl-prolyl cis-trans isomerase (mip) XF0652 peptidyl-prolyl cis-trans isomerase (slyD) XF0838 peptidyl-prolyl cis-trans isomerase (surA) XF1191 peptidyl-prolyl cis-trans isomerase (ppiD) XF1212 peptidyl-prolyl cis-trans isomerase (ppiB/ppi) XF1605 peptidyl-prolyl cis-trans isomerase XF0442 phosphatidyltransferase (ptr) XF0926 polypeptide deformylase (def/fms) XF2156 protein phosphatase (yloO) XF1446 protein transferase (aat) XF2585 protein-L-isoaspartate O-methyltransferase (pcm) XF1051 ribosome recycling factor (frr) XF2244 signal peptidase I (lepB) XF1437 thiol:disulfide interchange protein (dsbA) XF0353 translation initiation inhibitor 25%
29% 37% 23% 23% 37%
37% 22% 31% 30% 43% 28% 34% 43% 38% 42% 31%
XF0077 XF0078 XF0080 XF0369 XF0370 XF0371 XF0372 XF0373 XF0478
fimbrial adhesin precursor (mrkD) fimbrial adhesin precursor (mrkD) fimbrial adhesin precursor (fimA/pilA) fimbrial assembly membrane protein (pilM) fimbrial assembly membrane protein (pilN) fimbrial assembly membrane protein (pilO) fimbrial assembly protein (pilP) fimbrial assembly protein (pilQ) fimbrial assembly protein (pilY1)
CELL STRUCTURE/SURFACE STRUCTURES 30% 32% 29% 61% 44% 43% 38% 34% 33%
XF1289 2-dehydro-3-deoxyphosphooctonate aldolase (kdsA) 44% XF0105 3-deoxy-D-manno-octulosonic acid transferase (kdtA/waaA) 44% XF2299 3-deoxy-manno-octulosonate cytidylyltransferase (kdsB) 50% XF1419 acetyltransferase (lpxD/firA/omsA) 26% XF0918 acyl-[ACP]-UDP-N-acetylglucosamine (lpxA) 32% XF1994 beta 1,4 glucosyltransferase 29% XF0612 dolichol-phosphate mannosyltransferase (dmt) 24% XF1638 dolichyl-phosphate mannose synthase related protein 34% XF0257 dTDP-4-dehydrorhamnose 3,5-epimerase (rfbD) 75% XF0258 dTDP-4-keto-L-rhamnose reductase (rfbC) 54% XF0255 dTDP-glucose 4,6-dehydratase (rfbB) 76% XF0611 dTDP-glucose 4-6-dehydratase (rfbB) 63% XF1637 glycosyl transferase (spsQ) 29% XF1082 lipid A 4’-kinase (lpxK) 38% XF0104 lipid A biosynthesis lauroyl acyltransferase (htrB/waaM) 40% XF1348 lipid A biosynthesis lauroyl acyltransferase (htrB/waaM) 26% XF1042 lipid A disaccharide synthase (lpxB/pgsB) 45% XF0879 lipopolysaccharide biosynthesis protein (rfbU) 26% XF2434 lipopolysaccharide core biosynthesis protein 37% XF0980 lipopolysaccharide synthesis enzyme (kdtB) 56% XF0778 O-antigen acetylase (oafA) 26% XF1413 polysialic acid capsule expression protein (kpsF) 45% XF2154 saccharide biosynthesis regulatory protein (opsX) 73% XF0176 sugar transferase 43% XF1045 UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase (lpxD/firA/ssc) 41% XF1646 UDP-3-O-(R-3-hydroxymyristoyl)-glucosamine N-acyltransferase (lpxD/firA) 28% XF0486 UDP-3-O-[3-hydroxymyristoyl] glucosamine Nacyltransferase (lpxD) 31% XF0803 UDP-3-O-[3-hydroxymyristoyl] Nacetylglucosamine deacetylase (lpxC) 59% XF1415 UDP-N-acetylglucosamine 1carboxyvinyltransferase (murA/murZ) 62% XF1043 UDP-N-acetylglucosamine acyltransferase (lpxA) 44%
CELL STRUCTURE/SURFACE POLYSACCHARIDES, LIPOPOLYSACCHARIDES, AND ANTIGENS
XF0852 alanine racemase (alr) 45% XF0799 D-alanine--D-alanine ligase B (ddlB/ddl) 51% XF0855 lipoprotein (nlpD/lppB) 39% XF0416 lipoprotein precursor (vacJ) 36% XF1715 monofunctional biosynthetic peptidoglycan transglycosylase (mtgA) 50% XF0759 N-acetylmuramoyl-L-alanine amidase precursor (amiC) 45% XF2646 outer membrane lipoprotein precursor (lolB/hemM) 29% XF1896 outer membrane protein P6 precursor (pal/ompP6) 37% XF1614 penicillin binding protein (pbp4) 39% XF0368 penicillin-binding protein 1A (mrcA/ponA) 39% XF0884 penicillin-binding protein 1B (ponB) 41% XF1312 penicillin-binding protein 2 (mrdA/pbp2) 38% XF0792 penicillin-binding protein 3 (ftsI/pbpB) 43% XF0795 phospho-N-acetylmuramoyl-pentapeptidetransferase (mraY/murX) 59% XF2185 rare lipoprotein A (rlpA) 30% XF1309 rod shape-determining protein (mreB/envB/rodY) 77% XF1311 rod shape-determining protein (mreD) 32% XF0907 soluble lytic murein transglycosylase precursor (yjbJ) 42% XF0797 UDP-N-acetylglucosamine--N-acetylmuramyl(pentapeptide) pyrophosphoryl-undecaprenol (murG) 47% XF0798 UDP-N-acetylmuramate--alanine ligase (murC) 53% XF0276 UDP-N-acetylmuramate-L-alanine ligase (mpl) 50% XF1118 UDP-N-acetylmuramoylalanine--D-glutamate ligase (murD) 29% XF0793 UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase (murE) 43% XF0794 UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6 diaminopimelate--D-alanyl-D-alanyl ligase (murF/mra) 41% XF2572 UDP-N-acetylpyruvoylglucosamine reductase (murB) 43% XF1050 undecaprenyl pyrophosphate synthetase (uppS/rth) 51%
CELL STRUCTURE/MUREIN SACCULUS, PEPTIDOGLYCAN
outer membrane antigen (oma) outer membrane hemin receptor (phuR) outer membrane protein (mopB) outer membrane protein (ompW) outer membrane protein outer membrane protein (ompP1) outer membrane protein outer membrane protein (romA) outer membrane protein (smpA) outer membrane protein H.8 precursor outer membrane protein Slp precursor (slp) peptidoglycan-associated outer membrane lipoprotein precursor (pcp/lpp) XF0033 PilE protein (pilE) XF0975 polyphosphate-selective porin O (oprO) XF0321 porin O precursor (oprO) XF0028 pre-pilin like leader sequence (fimT) XF1363 soluble lytic murein transglycosylase precursor (slt/sltY)
XF1046 XF0384 XF0343 XF0872 XF0873 XF1053 XF1123 XF1739 XF2345 XF1024 XF1811 XF1547
fimbrial assembly protein (pilC) fimbrial protein fimbrial protein fimbrial subunit precursor fimbrillin fimbrillin fimbrillin (fimA) fimbrillin outer membrane usher protein precursor (fimD) pilus biogenesis protein (pilJ) pilus biogenesis protein (pilI) pilus biogenesis protein (pilB) pilus protein (pilG) PilX protein (pilX) PilY1 gene product (pilY1) PilY1 gene product (pilY1) pre-pilin leader peptidase (xpsO) pre-pilin leader sequence (pilV) twitching motility protein (pilU) twitching motility protein (pilT) type 4 fimbriae assembly protein (pilZ) type IV pilin (pilE) 36% 46% 33% 55% 82% 28% 32% 30% 76% 33% 60% 74% 62% 35%
56% 48% 53% 42% 37% 37% 38% 48%
43% 28% 43% 41%
61%
65%
46%
50% 49%
53% 64%
50%
67%
26%
35% 28% 35%
ABC transporter sodium permease (natB) ammonium transporter (amtB) bacterioferritin (bfr) cation:proton antiporter (ybaL) ferric enterobactin receptor (bfeA) ferric enterobactin receptor (bfeA) ferrous iron transport protein ferrous iron transport protein B (feoB) ion transporter magnesium and cobalt transport protein (corA) manganese transport protein (mntH2) Mg++ transporter (mgtE) Na+/H+ exchange protein Na+:H+ antiporter (yjcE) periplasmic iron-binding protein (afuA) polar amino acid transporter (ybeX) potassium uptake protein (kup/trkD) sodium ABC transporter ATP-binding protein (natA) TonB-dependent receptor for iron transport (ybiL) TonB-dependent receptor for iron transport (yncD) voltage-gated potassium channel beta subunit
50%
23%
47%
47%
33% 64% 26% 24% 42% 24% 46% 48%
27% 57% 61% 57% 22% 22% 47% 52% 48%
52% 53%
60% 40%
64% 66% 31% 48% 39% 36%
40% 37% 24%
XF2455 heme ABC transporter ATP-binding protein (ccmA) XF2456 heme ABC transporter membrane protein (ccmB) XF2457 heme ABC transporter membrane protein (ccmC) XF2261 oligopeptide transporter XF0806 preprotein translocase SecA subunit (secA/prlD/azi/pea) XF1172 preprotein translocase SecY subunit (secY/prlA) XF2639 preprotein translocase subunit (secE) XF0224 preprotein translocase YajC subunit (yajC) XF2685 protease IV (sppA) XF0225 protein-export membrane protein (secD) XF0226 protein-export membrane protein (secF) XF0304 protein-export membrane protein (secG) XF1801 protein-export protein (secB) XF0562 sec-independent protein translocase (tatC/mttB) XF0073 signal recognition particle protein (ffh)
47% 63%
55% 33% 36% 40% 44% 38% 43% 43%
60%
48% 40%
50%
41%
CELLULAR PROCESSES/TRANSPORT/Protein, peptide secretion
XF0367
XF1496
XF0599
XF1015 XF1401 XF1398 XF2019 XF0324 XF0901 XF1903 XF2329
XF2328 XF1844 XF0395 XF2140 XF2134 XF2137 XF0932 XF0933 XF1426 XF0900
CELLULAR PROCESSES/TRANSPORT/Cations
XF2446 ABC transporter sugar permease XF2447 ABC transporter sugar permease (lacF) XF2448 ABC transporter sugar-binding protein (malE) XF0087 alpha-ketoglutarate permease symporter (kgtP/witA) XF0976 C4-dicarboxylate transport protein (dctA) XF1462 glucose/galactose transporter (gluP) XF1609 glucose/galactose transporter (gluP) XF2267 glycerol uptake facilitator protein (glpF) XF1406 HPr kinase/phosphatase (ptsK) XF0320 Mg++/citrate complex transporter (citN/citH) XF1402 phosphotransferase system enzyme I (phbI) XF1403 phosphotransferase system HPr enzyme (phbH) XF1067 sugar ABC transporter ATP-binding protein
CELLULAR PROCESSES/TRANSPORT/Carbohydrates, organic acids, alcohols
XF0411 ABC transporter nitrate permease (nrtB) XF2141 ABC transporter phosphate binding protein (phoX) XF2142 ABC transporter phosphate permease (pstC/phoW) XF2143 ABC transporter phosphate permease (pstA/phoT) XF1344 ABC transporter sulfate binding protein (sbp) XF1345 ABC transporter sulfate permease (cysU/cysT) XF1346 ABC transporter sulfate permease (cysW) XF0412 nitrate ABC transporter ATP-binding protein (nrtD) XF2144 phosphate ABC transporter ATP-binding protein (pstB/phoT) XF1347 sulfate ABC transporter ATP-binding protein (cysA)
CELLULAR PROCESSES/TRANSPORT/Anions
XF0408 amino acid transporter (yhdG) XF2730 amino acid transporter (rhtC) XF2207 cationic amino acid transporter XF2208 cationic amino acid transporter XF1891 di-tripeptide ABC transporter membrane protein (yclF) XF0656 glutamate symport protein (gltT) XF1937 proton glutamate symport protein (gltP)
CELLULAR PROCESSES/TRANSPORT/Amino acids, amines
XF1953 XF1954 XF2544 XF1955 XF0031 XF0032 XF1224 XF2537 XF0029 XF1632 XF1633 XF0677 XF0479
XF2538 XF2539 XF2542 XF0083 XF0487 XF0538 XF0539 XF1791 XF0081 XF0875 XF0944 XF1077 XF1081 XF1223 XF1302 XF1409 XF1475
46%
ABC transporter ATP-binding protein (yusC) 48% ABC transporter ATP-binding protein (yjjK) 69% ABC transporter ATP-binding protein (ycfV) 55% ABC transporter ATP-binding protein (msbA) 41% ABC transporter ATP-binding protein (yadG) 54% ABC transporter ATP-binding protein 42% ABC transporter ATP-binding protein 60% AB
CELLULAR PROCESSES/TRANSPORT/Other
XF1913 type V secretory pathway protein (mttC)
articles
159