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Oct 24, 2013 - demonstrated that excretion of L-xylulose increases from milli- gram to gram ..... It was observed that xylose reductase (XR) activity was superior.
http://informahealthcare.com/ijf ISSN: 0963-7486 (print), 1465-3478 (electronic) Int J Food Sci Nutr, Early Online: 1–9 ! 2013 Informa UK Ltd. DOI: 10.3109/09637486.2013.845651

COMPREHENSIVE REVIEW

A review on different modes and methods for yielding a pentose sugar: xylitol Hansa Jain1 and Sanjyot Mulay2 Department of Pedodontics, Harsaran Dass Dental College, Ghaziabad, Uttar Pradesh, India and 2Department of Endodontics and Conservative Dentistry, Dr. D. Y. Patil Dental College and Hospital, Pune, Maharashtra, India

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Abstract

Keywords

Xylitol, a five-carbon polyalcohol, holds a substantial place in the cure and prevention of a number of diseases. The foremost reason for its lesser usage in day-to-day practice is its cost. The method employed on large scale production of this polyol, i.e. chemical reduction, uses extensive machinery and expensive chemicals thus increasing the basic cost of the sugar. Yield of xylitol by other methods including fermentation and enzymatic production is far less than chemical reduction. We did a literature analysis and briefed out the various experiments carried out till date and concluded on the required studies for improving its production and lowering down its cost.

Bacteria, chemical reduction, filamentous fungi, production, xylitol, yeast

Introduction Xylitol, a five-carbon sugar alcohol was discovered by a German professor Emil Herman Fisher in September 1890. He along with his assistant Rudolf Stahal separated xylitol from beech chips and named it xylit, which is the German name for xylitol. In the same era, French chemist M. G. Bertrand managed to isolate the syrup of xylitol by processing wheat and oat straw (Carson et al., 1943; Ma¨kinen, 2000). Touster et al. (1956) found that the metabolism of xylitol is related to pentosuria in human beings. His work demonstrated that excretion of L-xylulose increases from milligram to gram when observed first in non pentosuric individuals followed by pentosuric patients. His study also presented that the conversion of L-xylulose and xylitol requires a mitochondrial xylitol dehydrogenases, an nicotinamide adenine dinucleotide phosphate (NADP)-linked enzyme catalyzing the conversion of Lxylulose and xylitol. The enzyme is localized in both hepatic mitochondria and cytoplasm. It was also observed that xylitol could be further converted to D-xylulose by a nicotinamide adenine dinucleotide (NAD)-linked polyol dehydrogenase (McCormick & Touster, 1957; Touster, 1960), and D-xylulose is phosphorylated to D-xylulose-5-phosohate, which is a metabolite of the pentose phosphate cycle. All these observation led to the conclusion that xylitol is a physiological metabolite of the uronic acid cycle; the function of this pathway in humans is to produce glucuronic acid for synthetic processes and detoxification reactions thus claiming that xylitol is an endogenous intermediate of a physiological metabolic pathway in the human liver (Touster, 1974; Touster & Shaw, 1962). Later, it was observed that an adult human produces up to 15 g of xylitol per day in the liver. Its absorption takes place by passive

Correspondence: Dr. Hansa Jain, Lecturer, Department of Pedodontics, Harsaran Dass Dental College, Ghaziabad, Uttar Pradesh, India. Tel: +919760121286. E-mail: [email protected] and [email protected]

History Received 29 April 2013 Revised 14 July 2013 Accepted 4 September 2013 Published online 24 October 2013

or facilitated diffusion through the intestinal mucosa (Bassler et al., 1966). Due to its slow absorption and rapid metabolism in the liver, the blood concentrations of xylitol are low after oral administration. On intake of 1 gm of xylitol per kilogram of body weight, the maximal concentrations of xylitol in blood is less than 1 mM/l as observed (Ylikahri & Leino, 1979), and the concentration of xylitol is in the range between 0.03 and 0.06 mg/100 ml of blood (during normal metabolism) (Touster, 1969). The chemical formula of xylitol is C5H12O5, and it was originally reported that it has two crystalline forms, i.e. the stable rhombic form and the unstable monoclinic form; however, the monoclinic form was not reproduced later. The color of xylitol crystals is white, they are odorless and slightly hygroscopic. It has a negative heat of solution, which is about 145 kJ/kg, this causes a fresh feeling on coming in contact with saliva. Density of xylitol is 1520 kg/m3 and melting point ranges between 92  C and 96  C and it has high solubility in water whereas low solubility in methanol, ethanol and 2-propanol (Kim & Jeffrey, 1969; Rivas et al., 2006). The most compelling properties of xylitol in medicine are its insulin dependent metabolism, coequal sweetness to sucrose with lower energy value, i.e. 2.4 cal/g and its antibacterial properties. Sweetening power of xylitol is approximately twice to that of sorbitol and three times to that of mannitol. Because of its high sweetening power and no insulin requirement for digestion, xylitol has recently become an attractive alternative sweetener in the treatment of diabetes and glucose-6-phosphate dehydrogenasedeficient diseases. It can also be used in post-traumatic states or post-operative when there is increase in secretion of stress hormones, this leads to insulin resistance, which further causes inhibition of efficient glucose utilization. It has the potential to prevent osteoporosis, replace antibiotics in the treatment of otitis, and for this reason its chewing gum are given to children suffering from ear infections. Xylitol is competent of intervening in the initial steps of infections in patients with cystic fibrosis and decreases the pathogenicity of streptococcus pneumonia and

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mutans streptococci. Xylitol also prevents the adherence of pneumococci and Haemophilus influenza to nasopharyngeal cells. Due to its effect on mutans streptococci, it is used as an anticariogenic agent; it not only reduces the growth of this species but also disturbs its protein synthesis and causes ultrastructural changes in them (Beutler, 1984; Chen et al., 2010; Forster, 1974; Tapiainen et al., 2003). Xylitol is used in the food industry as the content of formulation used for storage because xylitol does not undergo Maillard reaction thus preventing the reduction of the nutritional value of the proteins. It is used for preparation of jams, jellies, marmalades, desserts and relishes and in the manufacture of sugarless chocolates, chewing gums, hard caramels, licorice sweets, wafer fillings, chocolates, pastilles and other confectioneries of diabetics (Bar, 1991; Emodi, 1978). It has been approved for use in food in over 50 countries worldwide and has already been used in the food industry for more than three decades (Povelainen, 2008).

Occurrence of xylitol Xylitol is a naturally occurring polyol found in lichens, seaweed and in a number of fruits and vegetables. It is also found in hardwoods and in agricultural and agro-based materials. The xylitol that is manufactured on commercial basis is similar in structure and properties to the one obtained from nature (Tables 1–3) (da Silva & Chandel, 2012; Gare, 2003).

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Table 1. Xylitol value of different foods (dry substance) (Gare, 2003).

Source Yellow plum Strawberry Cauliflower Lamb’s lettuce Raspberry Endive Eggplant Lettuce White mushroom Spinach Pumpkin Kohlrabi Fennel Onion Carrot Leek Banana Chestnut

Production of xylitol First large-scale production of xylitol was started in 1975 in Finland. Before this, it was manufactured in Italy, Germany, the Soviet Union, Japan and China. Amongst all these countries, Soviet Union produced the largest quantity of xylitol sugars. Total world production was estimated to be under 2000 tons/yr. All the aforementioned countries were producing it for its use in domestic market; and in Japan, it was used as an intravenous infusion to resuscitate patients from diabetic coma. In 1975, Finnish Sugar Co. Ltd. started large-scale production of xylitol in Kotka, Finland. This company had the capacity of over 3000 tons/year. One year later in 1976, Finnish Sugar Co. Ltd. went for a joint venture with a Swiss company F. Hoffman La-Roche and renamed the company as Xyrofin (Gare, 2003; Hyvonen et al., 1982). There are two methods of producing xylitol (1) Chemical reduction (2) Microbial (a) Fermentation (i) Yeast (ii) Fungi (iii) Bacteria (b) Enzymatic

Rowan berry Apple (Malus) Grape Red currant Bog whortleberry Banana Sea buckthorn Cloudberry Black currant Apple (Astrakan) Red whortleberry Plums Bilberry Cranberry Prunes

Lignocellulosic biomass is the basic material from which xylitol is extracted. It includes various agricultural residues, deciduous and coniferous woods, wastes from the pulp and paper industry and herbaceous energy crops. Its composition varies depending on the content present in it. The major components are cellulose, hemicelluloses and lignin (Table 4). Hemicelluloses are the second most common polysaccharides in nature. They are heterogeneous polymers of pentoses (xylose and arabinose), hexoses (mannose, glucose and galactose) and sugar acids. Celluloses are chemically homogenous, whereas hemicelluloses are chemically heterogeneous. Hemicelluloses can be divided into either derived from hardwood or from softwood; hardwood hemicelluloses contain mostly xylans and softwood

935 362 300 273 268 258 180 131 128 107 96.5 94 92 89 86.5 53 21 14

Table 2. Xylitol value of different foods (wet weight) (da Silva & Chandel, 2012).

Source

Chemical reduction

Xylitol content (mg/100 g, dry substance)

Xylitol content (mg/100 g, wet weight) 16 12.8 10.5 10 10 9.3 9.1 8.5 7 6.7 6.4 5.3 3.8 3.7 2

Table 3. Xylitol content of agro-industrial wastes (da Silva & Chandel, 2012).

Raw material Pistachio shells Barley bran Corn cobs Oak Corn fiber Sorghum straw Sugarcane bagasse Wheat straw Birch Aspen Poplar Brewery’s spent grain Corn stover Rice straw Eucalypt Vineshoot trimming Distilled grape marc

Xylitol content (mg/100 g) 33–50 29.2 28–35.3 21.7 21.6 21.5 20.5–25.6 19.2–21 18.5–24.9 18–27.3 17.7–21.2 15–23.4 14.8–25 14.8–23 14–19.1 12.8 8.3

Different modes and methods for yielding xylitol

DOI: 10.3109/09637486.2013.845651

Table 4. Composition of different lignocellulosic material (Saha, 2003). Composition (% dry basis)

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Corn fiber (20% starch) Corn cob Corn stover Rice straw Wheat straw Sugarcane bagasse Switchgrass Coastal bermuda grass

Cellulose

Hemicellulose

Lignin

15 45 40 35 30 40 45 25

35 35 25 25 50 24 30 35

8 15 17 12 20 25 12 6

hemicelluloses contain mostly glucomannans. Xylans present in most of the plant are heteropolysaccharides, which are linked by chains of 1-4-linked b-D-xylopyranose units. Along with xylose, arabinose, glucuronic acid or its 4-O-methyl ether and acetic, ferulic and p-coumaric acids are its other contents. Xylitol is produced from the xylose derived mainly from wood hydrolysates (Saha, 2003). Hydrolysis of lignocellulosic material for the production of polyols have been described since 1931 in US patent no. 1824221 in which small wood chips were subjected to high pressure and temperature for 30–35 s in the presence of steam, and then the material was discharged into a zone of low pressure passing though a constricted opening. This led to the formation of pentosans, lignin, hexosans, non-sugar carbohydrates and gum from the hydrolysate and further produces mannose, arabinose, galactose, glucose and xylose upon treatment. The procedure was not adapted for commercial use because the yield and the purity of the sugars were not of commercial significance. In 1956, another method described by Saums & Schoen (US patent no. 2759856) also related to the formation of wood sugars from lignocellulosic biomass. The process involved filtration of liquors obtained from hydrolyzed lignocellulose and then subjecting it to acid hydrolysis under high temperature and superatmospheric conditions for a time period of about 18–30 min. The process resulted in the formation of mixture of simple sugars, mannose, arabinose, galactose, glucose and xylose and the purity of mixed sugars achieved was about 85% (Saums & Schoen, 1956). Later, Apel (1961) described (US patent no. 2989569) a method of producing polyols from wood sugars, the process involved two steps, first hydrogenation at temperatures of about 40–90  C to a hydrogenation degree of 75–95% and completion of hydrogenation in the second step at temperatures higher than the first step but not exceeding 130  C and pressure being in the range of 10–100 atm. A process was carried out using the same example, and the process yielded large amount of highly purity xylitol, i.e. 65% of polyol with 80% of xylitol. Kohno & Yamatsu (1971) patented a process for production of xylitol (US patent no. 3558725) by catalytic hydrogenation of a xylose-containing solution derived from hydrolysis of lignocellulosic biomass. This process yields about 35–40% of xylitol and involved four steps; in the first step, cotton seed hulls were degraded by hydrolyzing to form crude solution containing predominantly xylose. The procedure utilized a dilute mineral acid-like sulfuric acid or hydrochloric acid, preferably sulfuric acid, as it is less corrosive toward the apparatus used than hydrochloric acid. Following this step, the crude solution was purified by first contacting with an acid cation exchange resin and then with an anion exchange resin of medium basicity, followed by the concentration of the purified solution. Following step included catalytic hydrogenation using raney nickel of the purified xylose containing concentrate to form the xylitolcontaining solution. Last step was the recovery of the xylitol from the solution.

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The basic disadvantage of these processes was cost ineffectiveness due expensive purification, for this, other methods of purification were implemented by other researchers like purification using ion exclusion techniques and chromatographic fractionation. A method patented in 1977, US patent no. 4008285 for the production of xylitol from xylan-containing raw materials. The method utilized acid hydrolysis for obtaining pentose-rich solution from the raw material and then purified it by mechanical filtration and ion exclusion techniques for the removal of color and desalting. The resulted solution was then fractionated using chromatographic fractionation to obtain a highly purified xylose solution. In the next step, this solution was further treated to recover xylitol. The method used for obtaining xylitol was chromatographic fractionation. Chromatographic fractionation includes passing the solution through a column of an alkaline earth metal salt of a polystyrene sulfonate cation exchange resin cross coupled with di-vinyl benzene (Melaja & Lauri, 1977). A year later, Melaja et al. (1978) described a method for preparing xylitol from an aqueous solution containing a mixture of polyols. The process had two steps, one was removal of the salt, sodium sulfate and the major part of the organic impurities and coloring bodies with ion-exclusion techniques, while a second stage accomplished final color removal. To improve the purification, a third step was added to after these two, it was the use of a synthetic macroreticular adsorbent such as Amberlite XAD2 to remove organic impurities. The macroreticular adsorbent purification was either used between the mentioned steps, i.e. immediately after ion-exclusion and before ion exchange step or as final purification procedure. Beck et al. (1998) patented a method to produce xylitol from gluconic acid. The procedure involved first obtaining gluconic acid either through catalytic oxidation or through fermentation of glucose. Then it was converted to arabinose, which has an advantage over arabinonic acid used in other methods, as, the former can be purified easily by ion exchange method than the latter. In the next step, the obtained arabinose was hydrogenated under mild reaction condition using a catalyst, preferably ruthenium or nickel. The temperatures used were between 70  C and 150  C with pressure between 0.1 and 10 MPa. This step led to the formation of D-arabinitol, which was further subjected to catalytic isomerization at elevated temperature and pressure to form a mixture of xylitol, ribitol and D,L-arabinitol. This mixture was refined using chromatography and led to yielding of xylitol with a purity of more than 95%. The advantages described in the invention were easier purification as use of arabinose rather than arabinonic acid and a shorter duration reaction when compared to invention using microorganism for conversion of glucose to xylitol. In another method, xylitol was obtained from a mixture of xylose and xylonic acid, which are found in sulfite cooking liquor. Sulfite cooking liquor contains insoluble wood material, lignin, hexose and pentose sugars, organic acids and cooking chemicals. The preferred cooking liquor used was magnesium sulfite cook, reason being that cations other than magnesium can be returned to the chemical circulation in the cellulose production. In the procedure, the magnesium sulfite cook was subjected to chromatographic separation with the use of magnesium separation resin to produce mixture containing xylose rich fraction, mixed fraction and a residual fraction in magnesium form. The xylose rich fraction was chromatographed with the use of separation resin. The separated xylose and xylonic acid were reduced catalytically or by metal hydride like sodium borohydride. This obtained material was further purified to obtain xylitol. The mentioned invention was advantageous as it was able to reduce the overall cost of the production, and there was enhanced use of the raw material (Heikkila et al., 1999).

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Heikkila et al. (2005) patented a process in which they used as an intermediate to produce xylitol. The process first involved preparation of L-xylose; the obtained L-xylulose was purified and was further used to produce xylitol. The purity of xylitol obtained was above 95%. Advantages of the chemical process for production of xylitol includes its usage in industrial manufacture of the polyol and the disadvantages includes use of high temperatures and pressures along with heavy machinery and processes for purification of the sugars due to the formation of byproducts. L-xylose

Microbial production

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Fermentation Production using yeast. Yeast has been considered the foremost choice amongst microorganisms for producing xylitol. Onishi & Suzuki (1969) screened 128 yeast strains for production of xylitol from glucose. As reported, it was the first study testing xylitol production from glucose by yeast. The selected 128 yeast strains were divided into three groups depending upon the pentitol produced. Among them, 27 were put in the group producing xylitol, and amongst them Candida guilliermondii ATCC20216 showed the most rapid fermentation. The process was a three-step fermentation procedure followed by isolation and purification of the xylitol for further use. Debaryomyces hansenii ATCC 20212 was employed in the first step, the step included conversion of glucose to D-arabitol. The method used a modified medium, which contained 15% glucose and 4% corn steep liquor. After 4 days of incubation period, 5.9 g of D-arabitol was accumulated per 100 ml of the broth. The obtained D-arabitol was 42.9% of the glucose consumed. After the complete exhaustion of glucose, the pH fermented broth was adjusted to 6.0 with addition of sodium hydroxide and sterilizing by autoclaving at 120  C for 15 min thus making broth favorable for production of Acetobacter suboxydans. A. suboxydans oxidized the D-arabitol to D-xylose when kept at 30  C for 2 days. C. guilliermondii was further used to reduce D-xylulose to xylitol. In 54 h, 1.5 g of xylitol was produced from 3.6 g of D-xylulose per 100 ml of the broth. As noted, the yield of the xylitol was approximately 15–20% (Table 5). Ten yeast strains were observed for xylose conversion to xylitol by Gong et al. (1981), and Candida tropicalis HPX2 produced the highest xylitol yield of 0.8 g/g of xylose. In an experiment, Gong et al. (1983) screened 20 strains of 11 species of Candida, 21 strains of eight species of Saccharomyces and 8 strains of Schizosaccharomyces pombe. The Candida sp. yielded xylitol (10–15% w/v). Later in a study conducted by Dominguez et al. (1996), which compared six yeast strains, D. hansenii gave a yield of 0.71 g/g. Further studies were carried out to increase the yield so that microbial production of xylitol could be used on industrial level. Cao et al. (1994) tried to increase xylitol production by testing the effect of increasing yeast cell density; the study showed that yield can be increased up to 81% of the theoretical value. Effect of the acetic acid concentration on xylose fermentation to xylitol was evaluated in semisynthetic medium in another study. The study indicated that increasing acetic acid concentration up to 1 g/l favored xylitol yield and productivity with maximum values of 0.82 g/g and 0.57 g/l/h (Felipe et al., 1995). In an experiment by Oh & Kim (1998), different ratios of xylose and glucose for feeding were tested to increase the yield. It was observed that the maximum xylitol from 300 g/l xylose was 91% at a glucose/xylose feeding ratio of 15%, while the maximum volumetric production rate of xylitol was 3.98 g/l/h at a glucose/xylose feeding ratio of 20%. de Carvalho et al. (2000) tested the effect of immobilized Candida cells on xylitol production. The results presented that the

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Table 5. Xylitol yield by different strains of yeast (Onishi & Suzuki, 1969).

Strain Saccharomyces rouxii N28 S. rouxii E7 S. rouxii 3281 S. rouxii 3292 S. rouxii 3215 S. rouxii 3217 S. rouxii 3219 S. rouxii 3221 S. rouxii 3222 S. rouxii 3224 S. rouxii var. halomembranis A31 Saccharomyces acidifaciens S9 S. acidifaciens var. halomembranis H3 Saccharomyces mellis 3220 Debaryomyces hansenii (ATCC 20220) Pichia farinosa (ATCC 20210) P. farinosa (ATCC 20218) Hansenula anomala Hyptis suaveolens Endomycopsis chodatii Candida tropicalis (ATCC 20215) C. tropicalis 3540 C. guilliermondii var. soya (ATCC 20216) C. melibiosii (IFO 961) Candida sp. 3547 Candida sp. 3548 Cryptococcus neoformans

Fermentation Xylitol produced time (d) (grams per 100 ml) 5 5 5 5 7 5 6 7 5 5 5 5 5 7 4 3 6 4 3 3 4 3 3 3 3 4 4

0.3 0.8 1.1 0.1 0.4 0.2 0.9 0.7 1.2 0.2 0.5 1.4 0.6 0.6 1.5 0.6 0.8 0.3 0.5 0.3 0.8 1.1 1.0 0.7 0.7 0.7 0.2

values of parameters increased significantly. The highest value of xylitol final concentration was 11.05 g/l; yield factor 0.47 g/g and volumetric productivity of 0.22 g/l/h were obtained. Later recycle fermentations of long-term cells of C. tropicalis were carried out. The average xylitol concentrations, fermentation time, volumetric productivities and product yields of all rounds carried out were evaluated. The study presented that using cell recycle fermentation along with chemically defined medium xylitol yield was increased as compared to batch fermentation (Kim et al., 2004). The effect of oxygenation was tested by Rivas et al. (2003), the results indicated that the highest xylitol concentration and volumetric productivity was obtained semi-aerobically. The concentration achieved was 71 g/l and volumetric productivity gained 1.5 g/l/h. In another study, its production by Pichia stipitis FPL-YS30 was investigated under aerobic and oxygen limited conditions. P. stipitis FPL-YS30 is a Xyl3-delta 1 mutant, which metabolizes xylose using an alternative metabolic pathway. It was observed that the mutant strain exhibited a higher volumetric productivity under aerobic conditions (Jin et al., 2005). Ding & Xia (2006) tested the effects of different aeration conditions. In the first phase, high aeration was applied resulting in rapid consumption of glucose and increase in biomass. In the second phase, aeration rate was reduced and it was observed that the yield of xylitol was improved. Effect of the age of inoculum was tested, and it was observed that it plays an important role in affecting the metabolic activity and viability of cells (du Preez, 1994; Sreenath et al., 1986). In an experiment by Sreenath et al. (1986), they observed that a 24-hold inoculum of Candida shehatae produced 20 g/l after 22 h with an yield of 0.24 g/g, whereas a 72-h-old inoculum produced only 9 g/l xylitol after 65 h with a yield of 0.13 g/g. Productivity and cell growth were favorable when inoculum age was 15 h–24 h for C. guilliermondii when tested by Pfeifer et al. (1996). These prove that lesser age of inoculums is more preferable for obtaining better yields of xylitol. On analyzing the effect of initial pH for xylitol

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DOI: 10.3109/09637486.2013.845651

production, it was reported that the value of pH to be used depended on the microorganism selected for the procedure, optimum range being 4–7. The different pH for different organism were pH 4 for C. tropicalis (Yahashi et al., 1996), pH 4.5 for C. shehatae (Kastner et al., 1996), pH 4–5.5 for Candida parapsilosis (Nolleau et al., 1995), pH 4–6 for Candida sp. (Cao et al., 1994), pH 5.5 for D. hansenii (Dominguez et al., 1996), pH 6 for C guilliermondii (Nolleau et al., 1995) and pH 7 for Candida boidinii (Vandeska et al., 1995). It has been observed that xylitol is produced by most yeast at temperature range of 24–45  C, and the optimum temperature range observed is 28–30  C (Barbosa et al., 1990; Cao et al., 1994). Later, workers started focusing on genetic engineering of the organism to improve the production. Rao et al. (2006) treated C. tropicalis with ultraviolet rays to produce mutants of C. tropicalis. The mutants were screened for xylitol production. Of all the mutants produced, UV1 yielded 0.81 g of xylitol per gram of xylose, and UV1 was further mutated with N-methyl-N0 nitro-N-nitroguanidine. After the screening of all the mutants, one of them, CTOMV5, produced 0.85 g/g of xylitol from xylose. It was observed that xylose reductase (XR) activity was superior in mutant CTOMVS than the wild strain, and the study also demonstrated that mutagenesis produced a superior xylitol producing strain. Another mutation study was carried out by Ko et al. (2006); in this experiment, two copies of XYL2 gene encoding xylitol dehydrogenase in C. tropicalis were sequentially disrupted using the Ura-blasting method. Ninety-eight percent of xylitol yield was achieved proving that mutation improves xylitol producing ability of C. tropicalis. In 2013, Jeon et al. integrated heterologous xylose transporter gene, At5g17017, into the genome of C. tropicalis, strain LXU1. At5g17017 was selected because it has high affinity for xylose and was codon optimized for functional expression in C. tropicalis. This resulted in increased uptake of xylose and higher xylitol volumetric production. The studies quoted indicate that by using genetic engineering and variations in the process, yield by Candida can be increased. Saccharomyces cerevisiae is a wild-type strain of yeast lacking D-xylose metabolic pathway, due to which it was considered to be a non-xylose fermenting yeast. But few of its properties including GRAS status, i.e. generally recognized as safe, and its strong tolerance to inhibitors present in lignocellulosic hydrolysates attracted many researchers to work on it. A recombinant S. cerevisiae strain was constructed by introduction of xylitol metabolism requisite gene into it. Later in 1991, under the control of the phosphoglycerate kinase promoter, XR gene was cloned from P. stipitis CBS 6054 and was transformed into S. cerevisiae. The conversion ratio of D-xylose to D-xylitol in this recombinant strain reached over 95%. A XR gene was cloned from C. guilliermondii ATCC 20118, and the gene was expressed in methylotrophic yeast Pichia pastoris under the control of an alcohol oxidase promoter. The resulting strain was able to accumulate D-xylitol and when grown in aerobic conditions could give high yields (7.8 g/l) (Chen et al., 2010). Kim et al. (1999) studied production of xylitol from xylose by using recombinant S. cerevisiae 2805. The strain contained XR genes (XYL1) of P. stipitis at chromosomal delta sequence. About 40 copies of XYL1 gene were present on the chromosome of S. cerevisiae 2805-39-40, this strain was obtained by a sequential transformation using a dominant selection marker, neor, and an auxotrophic marker, URA3. The results presented that multiple XYL1 genes containing S. cerevisiae proved to be much more efficient for the long-term non-selective culture rather than S. cerevisiae, which harbors the episomal plasmid containing the XYL1 gene. In 2001, another experiment using XR gene was carried out. XYL1 was isolated from P. stipitis and C. shehatae

Different modes and methods for yielding xylitol

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and was cloned into YEP-based vectors under the control of ADH2 and PGK1 promoter/terminator cassettes. This was introduced into S. cerevisiae Y294 by electroporation. The recombinant strains converted xylose to xylitol with yields approaching the theoretical maxima (Govinden et al., 2001). Toivari et al. (2007) described single-step fermentation by recombinant S. cerevisiae strains. Trans-ketolase-deficient S. cerevisiae strains, which over express xylitol dehydrogenase and sugar phosphate phosphatase-encoding genes, were constructed. The phosphorylation of D-xylose to D-xylulose 5-phosphate was prevented by additionally deleting the endogenous xylulokinase-encoding gene. Expression of XYL2 of P. stipitis in the transketolase-deficient strain resulted in an 8.5-fold enhancement of the total amount of the ribitol and xylitol produced. Oh et al. (2013) engineered S. cerevisiae D-20-BT, which is capable of converting xylose to xylitol through simultaneous utilization of xylose and cellobiose. They engineered XR, cellodextrin transporter and produced xylitol via simultaneous utilization of cellobiose and xylose. The strain with co-consumption of cellobiose and xylose exhibited 40% higher volumetric xylitol production. The overexpression of S. cerevisiae ALD6, IDP2 or P. stipitis ZWF1 coding for cytosolic NADP(þ)dependent dehydrogenases increased the intracellular NADPH availability of the D-10-BT strain, which resulted in a 37–63% improvement in xylitol productivity thus presenting that xylitol production can be improved by co-utilization of cellobiose and xylose. Even after extensive work on S. cerevisiae to improve its production, Candida yeast are still considered superior choice due to their few distinct characteristics. These include consumption of D-xylose by natural process and maintenance of reduction– oxidation balance by them during D-xylitol accumulation, but opportunistic pathogenic nature of few Candida spp account for its inability to be used in food industry. Production using Fungi. Xylitol production by filamentous fungi was first described by Chiang & Knight (1960). They worked with Penicillium chrysogenum and found positive results. It has been observed that fungi play an important role in decomposition of high pentose-concentrated lignocellulosic residues. Fungi decompose this biomass through enzymatic depolymerization of the plant cell wall and subsequent consumption of the degradation products like D-xylose. Another reason for considering filamentous fungi is that they produce enzymes like xylanolytic complex. This enzyme is capable of converting residue to D-xylose with subsequent xylitol production by bioconversion. In a study by Sampaio et al. (2003), they studied 11 strains of filamentous fungi. Selected fungi included Penicillium roqueforti CCT 1273, Verticillium crustosum CCT 4034, Penicillium brevicompactum CCT 4457, P. chrysogenum CCT 1273, Penicillium purpurogenum CCT 2008, Penicillium citrinum CCT 3281, Penicillium janthinellum CCT 3162, Penicillium griseoroseum CCT 6421, Penicillium expansum VIC, Penicillium italicum DMBI and Aspergillus niger DMB2. The fungi were activated in oat-agar medium and incubated until sporulation occurred at 25  C; and after the growth of spores at 4  C, the spores were screened and a mineral medium was used for the screening purposes. The results presented that maximum xylitol production varied from 0.14 to 0.52 g/l with substrate consumption between 15 and 79%. Penicillium crustosum produced the highest mycelia mass with 76% D-xylose consumption. Diano et al. (2006) evaluated influence of oxygen availability, carbon and nitrogen sources on polyols synthesis in A. niger. During the fermentation process, high concentration of glucose and xylose served as carbon source, whereas ammonium or nitrate

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served as nitrogen source. The growth of biomass in the dispersed hyphae led to an increase of medium viscosity and decrease in mass transfer, especially affecting oxygen transfer. The consequence was switch between fully aerobic conditions and oxygen-limited conditions. Metabolite quantification showed that polyols were the main metabolic products formed and represented up to 22% of the carbon consumed in oxygen-limited conditions, and it was observed that the polyol concentration and the polyol pattern depended strongly on the environmental conditions. Later, Mudaliyar et al. (2011) tested a number of agro wastes as a substrate for bioproduction of xylitol. A total of six different types of agro-wastes including groundnut shells, coconut husk, jambulina leaves, grass straw, eucalyptus leaves and eucalyptus wood were treated to form hydrolysate followed by use of A. niger to produce xylitol through the process of fermentation. For the formation of hydrolysate, the raw material was first steamed in a 100 l autoclave at 121  C for 20 min, then water was added and boiled at 80  C for 30 min. After this, the hydrolysate was recovered and treated with acid hydrolysis. Acid hydrolysis was carried out to cleave the xylooligosaccharides into monomeric sugars. After acid hydrolysis, the hemicellulose hydrolysate was treated with alkaline solution to bring down its pH, and then the material was finally fermented with A. niger. One percent of A. niger inoculums was added to 500 ml of fermentation media for 6 days. It was observed that the highest yield was obtained was for grass straw, i.e. 0.092 g/l with (NH4)2SO4 as nitrogen source with initial pH of 5. Xylitol yield obtained using fungi lags far behind Candida with incomplete usage of the substrate. Literature lacks studies on metabolic engineering on fungi to enhance its potency to be used xylitol synthesis. Following reading on its marked properties like recycling of xylan-rich lignocellulosic agro-industrial residues, we warrant further studies on filamentous fungi. Production using bacteria. Around the year 1970, two scientists observed that thiamine-requiring strain of Corynebacterium accumulated a large amount of pyruvic acid, D,L-alanine and Dribulose extracellularly. This reaction was observed when the bacterium was grown on the thiamine-deficient medium containing gluconate as the sole carbon source. It was also found that the cells that were previously grown on gluconate-containing medium were found to utilize aldopentoses including D-xylose, D-ribose and L-arabinose and producing the corresponding pentitol with high yields. Keeping this in view, Yoshitake et al. conducted a study to identify pentitols produced by Corynebacterium. It was observed that the bacterium was able to produce corresponding pentitols after reacting with the pentoses. Other factors were also noted, such as the effect of cell growth, gluconic acid concentration, pentose concentration. The results presented that the sufficient growth of cells appeared to be required for the increased production of pentitols, and maximum yields of xylitol and ribitol were obtained at the gluconic acid concentration of 8.0% and 6– 8%, whereas production of L-arabitol was progressively increased with the increase of gluconic acid concentration for up to 12%. Highest yield of pentitols were observed with pentose concentration of 150 mg/ml (Yoshitake et al., 1971). The production of xylitol by bacteria using glucose was patented in 2001 (Takeuchi et al., 2001). The inventors searched for microorganisms that had an ability to convert D-xylulose to xylitol among acetic acid bacteria. They found genus Acetobacter and Gluconobacter acquiring the mentioned ability. The following example based on the invention presented nine strains of bacteria that yielded xylitol from glucose. In the procedure, a medium containing 0.2% of ammonium sulfate, 0.1% of potassium dihydrogenphosphate, 0.3% of dipotassium hydrogen phosphate,

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Table 6. Xylitol yield by different bacterial strains (Sugiyama et al., 2001; Takeuchi et al., 2001).

Bacterial strain Gluconobacter cerinus IFO 3262 Gluconobacter oxydans ATCC 8147 G. oxydans IFO 3292 G. oxydans subsp. Suboxydans IFO 3130 Acetobacter liquefaciens ATCC 14835 Acetobacter pasteurianus IFO 3222 A. pasteurianus IFO 3223 Achromobacter Viscosus ATCC 12448 Agrobacterium tumefaciens ATCC 2778 Agrobacterium radiobacter ATCC 4718 Agrobacterium paraffineus ATCC 15590 A. paraffineus ATCC 15591 A. paraffineus ATCC 19064 A. paraffineus ATCC 19065 Agrobacterium hydrocarboglutamicus ATCC 15583 Azotobacter indicus ATCC 9037 Brevibacterium ketoglutamicum ATCC 15587 B. ketoglutamicum ATCC 15588 Corynebacterium fasciens IAM 1079 Erwinia amylovora IFO 12687 Flavobacterium peregrinum CCM 1080-A Flavobacterium fucatum FERM P-7053 Micrococcus sp. CCM 825 Nocardia opaca NCIB 9409 Planococcus eucinatus FERM P-9133 Pseudomonas synxantha ATCC 796 Rhodococcus erythropolis ATCC 11048 Morganella morganii AJ 2771 Actinomadura madurae ATCC 19425 Actinomyces violaceochromogenes IFO 13100 Streptomyces coelicolor ATCC 10147 Streptomyces flavelus AJ9012 Streptomyces griseolus NRRL B-1062 Streptomyces lividans IFO 13385 Streptomyces olivaceus ATCC 21379 Streptomyces tanashiensis ATCC 15238 Streptomyces virginiae AJ9053 Streptomyces antibiotics NRRl 3238 Streptomyces cacaoi ATCC 19093 Streptomyces lavendulae ATCC 8664

Xylitol produced (g/l) 0.3 0.4 0.3 0.4 0.5 0.4 0.3 0.1 0.3 0.6 2.6 4.4 3.7 3.6 4.0 0.3 2.2 3.4 1.6 4.3 0.3 1.2 0.2 3.8 0.5 0.2 5.5 1.7 0.5 0.1 0.5 0.3 0.4 0.4 0.3 0.9 0.5 0.1 0.1 0.1

0.5% of magnesium sulfate and 0.5% of yeast extract at pH 6.0 was introduced in the test tubes. Each test tube was filled with 4 ml solution, was sterilized by heating at 120  C for 20 min and D-glucose was added to the medium at the concentration of 5%. The selected strains were inoculated to the medium and were cultured at 30  C for 24 h. The culture obtained was used as a seed culture, and same composition medium was introduced into 500 ml Sakaguchi flasks and were sterilized at 120  C temperature for about 20 min. The seed culture was inoculated into this medium at a concentration of 2% and was cultured for 4 days at 30  C. After this, xylitol yield was quantified, and it was observed that highest yield was obtained from Acetobacter aceti subsp xylinum ATCC14851 and Acetobacter liquefaciens ATCC14835 i.e. 0.5 g/l (Table 6). The process of producing xylitol from D-arabitol using microorganism belonging to the genus Gluconobacter or Acetobacter, Achromobacter, Agrobacterium, Arthrobacter, Azotobacter, Brevibacterium, Corynebacterium, Erwinia, Flavobacterium, Micrococcus, Nocardia, Planococcus, Pseudomonas or Rhodococcus, Morganella, Actinomadura, Actinomyces or Streptomyces. Two experiments using the invention explained the amount of xylitol produced by the bacterial strains tested. In one experiment, 4 ml of medium at pH 7 and containing 1.8% of normal bouillon was poured into a test tube.

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This test tube was sterilized by heating at 120  C for 20 min. D-Arabitol, xylitol and D-xylose were separately sterilized and then added to the medium to give a concentration of 1%. The medium obtained was inoculated with the microorganisms and were incubated at 30  C for 2 d. The cultured cells were treated, and the resulting solution was distributed into test tubes. Then, 0.9 ml was added to each test tube, and each of the crude enzyme solution was added to this mixture and kept at 30  C, pH 8 for 22 min. Highest yield was achieved by Rhodococcus erythropolis ATCC11048, i.e. 5.5 g/l. Second experiment using the same invention was carried out with different strains and different medium. In 50 ml of medium at pH 7 containing 0.2% yeast extract, 0.2% meat extract, 0.4% peptone, 0.5% NaCl and 0.2% magnesium sulfate heptahydrate was put into flask and was sterilized at 120  C for 20 min. The following procedure was similar to earlier described experiment and among the tested strains Streptomyces tanashiensis ATCC15238, i.e. 0.9 g/l (Table 6) (Sugiyama et al., 2001). Later, a few studies have been carried out on Gluconobacter oxydans to improve its xylitol yield; in 2011, co-expression of plasmid-encoding xylitol dehydrogenase gene and cofactor regeneration enzyme gene were evaluated for production of xylitol. Two systems were created, in one glucose dehydrogenase gene from Bacillus subtilis and in second an alcohol dehydrogenase gene from G. oxydans. It was observed that the first system yield was higher than the second system but the production of xylitol from both the groups were more than threefold higher compared to that of the G. oxydans NH-10 cells (Zhou et al., 2012). Another study was carried out on G. oxydans, in which it was engineered to co-express the XDH gene and a glucose dehydrogenase gene from B. subtilis and a new strain G. oxydans PXPG was constructed. It was observed that activities for both enzymes were more than twofold higher in the G. oxydans PXPG than in the wild strain, thus concluding the increasing activity of XDH and the cofactor NADH supply improves the yield of xylitol (Zhang et al., 2013). Escherichia coli is the other bacterium considered for yielding high value of xylitol; for this reason, some experiments have been performed on improving production of the discussing polyols. In one of the study XR gene, xyrA of C. tropicalis IFO0618 was expressed in E. coli JM109. The results indicated that E. coli expressing xyrA gene successfully converted D-xylose to xylitol, and the yield of xylitol reached 13.3 g/l when cultivated for 20 h (Suzuki et al., 1999). It has been observed that deleting E. coli xylulokinase gene (XylB) is necessary for achieving high titers of xylitol from the xylitol producing strain of E. coli, and P. stipitis is a good source of xylulokinase (Xyl3). In a study, effect of Xyl3 and XylB on growth and xylitol production by engineered E. coli was evaluated, and it was observed that there was significant higher activity on xylitol by XylB when compared to Xyl3. It was also observed that replacement of Xyl3 resulted in drastic increase of xylitol titer (Akinterinwa & Cirino, 2009). E. coli ZUC99 (pATX210) was created by introduction of a bioconversion pathway consisting of three enzymes. Expression of the recombinant enzymes in the active form was achieved in the presence of L-arabinose. A xylitol production profile of the strain was evaluated, and it was observed that use of glycerol as co-substrate caused increase in xylitol production and it was exhibited efficient conversion in fermentor experiments with medium containing L-arabinose and glycerol (Sakakibara et al., 2009). In order to reduce formation of L-arabinose during conversion of D-xylose to xylitol by E. coli, E. coli was engineered and combined with a previously engineered XR mutant. The process resulted in total reduction of L-arabinitol formation, and the purity of xylitol production achieved was nearly 100% (Nair & Zhao, 2010).

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One experiment involving Corynebacterium glutamicum was performed by Sasaki et al. (2010) to enhance its ability to ferment xylitol. For this purpose, the pentose transporter gene (area) from Corynebacterium ATCC31831 was integrated into the C. glutamicum R chromosome. Consequent disruption of its lactate dehydrogenase gene and expression of single site mutant XR from Candida tenuis (CtXR(K274R)) resulted in recombinant C. glutamicum strain CtXR4. During the process of xylitol formation, a toxic intracellular material xylitol phosphate is formed and to eliminate its production genes XylB and phosphoenolpyruvate-dependent fructose phosphotransferase were disrupted to yield strain CtXR7. This resulted in 1.6-fold increase production of xylitol by strain CtRX7. Enzymatic production The process involving enzymatic involvement for production of xylitol includes conversion of xylose to xylitol using XR of Candida pelliculosa along with coupling it with the oxido reductase system of Methanobacterium sp. (Tran et al., 2004). Authors have observed that conversion of xylose to xylitol takes place stoichiometrically with an equivalent consumption of NADPH and that an almost quantitative conversion of xylose to xylitol was achieved using NADPþ to xylose ratio of over 1:30, whereas the coenzyme was successfully regenerated and retained using a membrane reactor. Approximately 90% of the conversion of xylose to xylitol was achieved at 35  C and pH 7.5 after a reaction time of 24 h (Rafiqul & Mimi Sakinah, 2012). Nidetzky et al. (1996) developed a process for enzymatic conversion of xylose to xylitol. An NADH-dependent XR from C. tenuis acted as a catalyst in the reduction of xylose. It was then coupled to enzymatic oxidation of D-glucose or D-xylose by glucose dehydrogenase from Bacillus cereus. This led to 10 000-fold regeneration of NADH per cycle of discontinuous conversion. In the process, using a simple kinetic model as a tool for process optimization of the substrate was converted to concentration of 300 g/l, with a 96% yield and xylitol produced was 3.33 g/l/h. Neuhauser et al. (1998) devised a procedure in which C. tenuis XR-mediated NADH-dependent XR coupled with formate dehydrogenase (FDH) from C. boidinii. FDH was supplied with formate to enable NADH-dependent reduction of xylose to xylitol by XR continuously. The process was carried out at 25  C temperatures with pH 7 in a 20 ml bioreactor. Fed batch conversion of 0.5 M (76 g/l) xylose into xylitol yielded productivity of 2.8 g/l during 20 h. Tran et al. (2004) used enzymatic production technique of xylitol production by hydrolyzing beech wood and walnut shells at 40  C with mixed crude enzyme produced by Penicillium sp. AHT-1 and Rhizomucor pusillus HHT-1. These two strains were observed to be highly potent producers of xylanotic enzymes. First xylose was produced from beech wood and walnut shells; the yield was 4.1 g and 15.1 per 100 g, respectively. Xylitol was produced using C. tropicalis IF00618 and waste product hydrolyzed solution. It was observed that the yield increased with addition of 1% yeast extract and 1% glucose at an initial concentration. The yield of xylitol obtained was about 50%. Active mutant phosphate dehydrogenase (12x-A176R PTDH) from Pseudomonas stutzeri was engineered to improve its potential as an effective NADPH regeneration. Two important enzymatic reactions including xylitol synthesis catalyzed by XR and phenyl ethanol synthesis catalyzed by alcohol dehydrogenase were analyzed. These two reactions were taken as model systems, and the mutant PTDH was directly compared to Pseudomonas sp. It was observed that catalytic efficiency was 70-fold higher; and for the continuous production of (R)-phenylethanol in the enzyme membrane reactor, the mean conversion of the 12x-A176R mutant

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was 98% compared to 70% for the mut Pse-FDH. Production of xylitol was twofold higher that the best yeast D-xylose converting strain, i.e. C. tropicalis and 20-fold higher that the most efficient continuous enzyme membrane reactor system as observed by the author (Johannes et al., 2007). Yoon et al. (2006) observed enzymatic production of pentoses from the hemicellulose fraction of corn residue. The corn husks and corn cobs were extracted to obtain hemicellulose fraction with 1.25 mol/NaOH. Rapidase pomaliq, an enzyme preparation derived from filamentous fungi A. niger and Trichoderma reesei was used as an enzyme source. The result indicated that Rapidase pomaliq increased the concentration of pentoses from an initial value of 106.5–210.6 g/Kg dry matter of corn husks and 8.6– 141.6 g/Kg dry matter of corn cobs. The reaction conditions were 50  C, at pH 5 for 8 h, thus proving that this enzyme can be used as a sole enzyme source for the production of pentose sugars. A study by Branco & Silva (2010) was carried out to enhance enzymatic xylitol production. They evaluated different concentration of Tris buffer for obtaining the highest xylitol yield. The most favorable conditions observed were 0.22 M initial concentration of the buffer yielded 0.31 g/l/h xylitol volumetric productivity with 99% xylose to xylitol conversion efficiency. Ricardo et al. tested the use of sugarcane bagasse hemicellulosic hydrolysate (SCBHH) as a source of sugars for enzymatic xylitol production. Different concentrations of treated SCBHH in the commercial reaction media were evaluated. A weak acid was used for the hydrolysis of sugarcane bagasse and yielded a hydrolysate with 18 g/l and 6 g/l of xylose and glucose. The conversion efficiency of xylose-xylitol observed was 100% in all the experiments tested hence proving that treated SCBHH can be suitable xylose and glucose source for the enzymatic xylitol production (de Freitas Branco et al., 2011). The number of studies that have been carried out on enzymatic process are too scarce to comment on it. Undoubtedly, the process seems to be promising, but further studies are required before it can be considered for industrial production. From the data quoted, it can be summarized that xylitol production using micro-organisms can replace chemical processes if further studies concentrating on excluding the drawbacks of the former processes are taken into consideration in future. Though the yield is markedly high, its cost ineffectiveness makes it unwanted. Seeing enormous advantages of xylitol, we warrant further studies and experiment to enhance its production using microbes. This may help yield higher production of xylitol at a much lower cost.

Acknowledgements The authors would like to thank Mrs. Parul Jain.

Declaration of interest The authors declare no conflict of interest and it was a self-funded research.

References Akinterinwa O, Cirino PC. 2009. Heterologous expression of Dxylulokinase from Pichia stipitis enables high levels of xylitol production by engineered Escherichia coli growing on xylose. Metab Eng 11:48–55. Apel A. 1961. Conversion of wood sugars to polyols. US patent 2989569. Bar A. 1991. Xylitol. In: Nabors LO, Gelardi RC, editors. Alternative sweetener. New York: Marcel Dekker Inc. p. 361–370. Barbosa MFS, Lee H, Schneider H, Forsberg CW. 1990. Temperature mediated changes of D-xylose metabolism in the yeast Pachyoslen tannophilus. FEMS Microbiol Lett 72:35–40.

Int J Food Sci Nutr, Early Online: 1–9

Bassler KH, Toussaint W, Stein G. 1966. Xylitol evaluation in premature infants, infants, children and adults. Kinetics of its elimination from the blood. Klin Wochenschr 44:212–215. Beck RHF, Elseviers M, Marianne S, Coomans J. 1998. Process for the production of xylitol. US patent 5714602. Beutler HO. 1984. Xylitol. In: Bergmeyer HU, editor. Methods of enzymatic analysis. Weinheim: Verlag Chemie. p. 484–490. Branco Rde F, Silva SS. 2010. Contribution of tris buffer on xylitol enzymatic production. Appl Biochem Biotechnol 162:1558–1563. Cao NJ, Tang R, Gong CS, Chen LF. 1994. The effect of cell density on the production of xylitol from D-xylose by yeast. Appl Biochem Biotechnol 45–46:515–519. Carson JF, Waisbrot SW, Jones FT. 1943. A new form of crystalline xylitol. J Am Chem Soc 65:1777–1778. Chen X, Jiang ZH, Chen S, Qin W. 2010. Microbial and bioconversion production of D-xylitol and its detection and application. Int J Biol Sci 6:834–844. Chiang C, Knight SG. 1960. A new pathway of pentose metabolism. Biochem Biophys Res Commun 3:554–559. da Silva SS, Chandel AK. 2012. D-Xylitol: fermentative production, application and commercialization. Sao Paulo, Brazil: Springer. de Carvalho W, da Silva SS, Vitolo M, de Mancilha IM. 2000. Use of immobilized Candida cells on xylitol production from sugarcane bagasse. Z Naturforsch C 55:213–217. de Freitas Branco R, dos Santos JC, da Silva SS. 2011. A novel use for sugarcane bagasse hemicellulosic fraction: xylitol enzymatic production. Biomass Bioenergy 35:3241–3246. Diano A, Bekker-Jensen S, Dynesen J, Nielsen J. 2006. Polyol synthesis in Aspergillus niger: influence of oxygen availability, carbon and nitrogen sources on the metabolism. Biotechnol Bioeng 94:899–908. Ding X, Xia L. 2006. Effect of aeration rate on production of xylitol from corncob hemicellulose hydrolysate. Appl Biochem Biotechnol 133: 263–270. Dominguez JM, Cao NJ, Gong CS, Tsao GT. 1996. Pretreatment of sugar cane bagasse hemicellulose hydrolysate for xylitol production by yeast. Appl Biochem Biotechnol 57/8:49–56. du Preez JC. 1994. Process parameters and environmental factors affecting D-xylose fermentation by yeasts. Enzyme Microb Technol 16:944–956. Emodi A. 1978. Xylitol: its properties and food applications. Food Technol 32:20–32. Forster H. 1974. Sugars in nutrition. New York: Academic Press. Felipe MG, Vieira DC, Vitolo M, Silva SS, Roberto IC, Manchilha IM. 1995. Effect of acetic acid on xylose fermentation to xylitol by Candida guilliermondii. J Basic Microbiol 35:171–177. Gare F. 2003. The sweet miracle of xylitol. California: Basic Health Publications, Inc. Gong CH, Chen LF, Tsao GT. 1981. Quantitative production of xylitol from D-xylose by a high xylitol producing yeast mutant Candida tropicalis HXP2. Biotechnol Lett 3:130–135. Gong CS, Glaypool TA, McCraken LD, Maun CM, Ueng PP, Tsao GT. 1983. Conversion of pentoses by yeasts. Biotech Bioeng 25: 85–102. Govinden R, Pillay B, van Zyl WH, Pillay D. 2001. Xylitol production by recombinant Saccharomyces cerevisiae expressing the Pichia stipitis and Candida shehatae XYL1 genes. Appl Microbiol Biotechnol 55: 76–80. Heikkila H, Ojamo H, Tylli M, Ravanko V, Nurmi J, Haimi P, Alen R, et al. 2005. Process for the production of xylitol. US patent 6894199 B2. Heikkila H, Puuppo O, Tylli M, Nikander H, Nygren J, Lindroos M, Eroma O. 1999. Method for producing xylitol. US patent 5998607. Hyvonen L, Koivistoinen P, Voirol F. 1982. Food technological evaluation of xylitol. In: Chichester CO, Mrak EM, Stewart G, editors. Advances in food research. Vol 28. New York: Academy press. p. 373–403. Johannes TW, Woodyer RD, Zhao H. 2007. Efficient regeneration of NADPH using an engineered phosphite dehydrogenase. Biotechnol Bioeng 96:18–26. Jeon WY, Shim WY, Lee SH, Choi JH, Kim JH. 2013. Effect of heterologous xylose transporter expression in Candida tropicalis on xylitol production rate. Bioprocess Biosyst Eng 36:809–817. Jin YS, Cruz J, Jeffries TW. 2005. Xylitol production by a Pichia stipitis D-xylulokinase mutant. Appl Microbiol Biotechnol 68:42–45.

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DOI: 10.3109/09637486.2013.845651

Kastner JR, Roberts RS, Jones WJ. 1996. Effect of pH on cell viability and product yields in D-xylose fermentations by Candida shehatae. Appl Microbiol Biotechnol 45:224–228. Kim YS, Kim SY, Kim JH, Kim SC. 1999. Xylitol production using recombinant Saccharomyces cerevisiae containing multiple xylose reductase genes at chromosomal delta-sequences. J Biotechnol 67: 159–171. Kim TB, Lee YJ, Kim P. 2004. Increased xylitol production rate during long-term cell recycle fermentation of Candida tropicalis. Biotechnol Lett 26:623–627. Kim HS, Jeffrey GA. 1969. The crystal structure of xylitol. Acta Cryst 25: 2607–2613. Ko BS, Kim J, Kim JH. 2006. Production of xylitol from D-xylose by a xylitol dehydrogenase gene-disrupted mutant of Candida tropicalis. Appl Environ Microbiol 72:4207–4213. Kohno S, Yamatsu I. 1971. Preparation of xylitol. US patent 3558725. Ma¨kinen KK. 2000. The rocky road of xylitol to its clinical application. J Dent Res 79:1352–1355. McCormick DB, Touster O. 1957. The Conversion in vivo of xylitol to glycogen via the pentose phosphate pathway. J Biol Chem 229: 451–461. Melaja AJ, Lauri H. 1977. Process for making xylitol. US patent 4008285. Melaja AJ, Virtanen JJ, Heikkila HO. 1978. Method for recovering xylitol. US patent 4066711. Mudaliyar P, Pandit P, Suryavanshi M. 2011. Screening of different agrowastes as substrates for xylitol production by Aspergillus niger. Asian J Exp Biol Sci 2:739–745. Nair NU, Zhao H. 2010. Selective reduction of xylose to xylitol from a mixture of hemicellulosic sugars. Metab Eng 12:462–468. Neuhauser W, Steininger M, Haltrich D, Kulbe KD, Nidetzky B. 1998. A pH-controlled fed batch process can overcome inhibition by formate in NADH-dependent enzymatic reductions using formate dehydrogenasecatalyzed coenzyme regeneration. Biotechnol Bioeng 60:277–282. Nidetzky B, Neuhauser W, Haltrich D, Kulbe KD. 1996. Continuous enzymatic production of xylitol simultaneous coenzyme regeneration in a charged membrane reactor. Biotechnol Bioeng 52:387–396. Nolleau Y, Preziosi-Belloy L, Navarro JM. 1995. The reduction of xylose to xylitol by Candida guilliermondii and Candida parapsilosis: incidence of oxygen and pH. Biotechnol Lett 17:417–422. Onishi H, Suzuki T. 1969. Microbial production of xylitol from glucose. Appl Microbiol 18:1031–1035. Oh DK, Kim SY. 1998. Increase of xylitol yield by feeding xylose and glucose in Candida tropicalis. Appl Microbiol Biotechnol 50:419–425. Oh EJ, Ha SJ, Rin Kim S, Lee WH, Galazka JM, Cate JH, Jin YS. 2013. Enhanced xylitol production through simultaneous co-utilization of cellobiose and xylose by engineered Saccharomyces cerevisiae. Metab Eng 15:226–234. Pfeifer MJ, Silva SS, Felipe MG, Roberto IC, Mancilha IM. 1996. Effect of culture conditions on xylitol production by Candida guilliermondii FTI 20037. Appl Biochem Biotechnol 57–58:423–430. Povelainen M. 2008. Pentitol phosphate dehydrogenases: discovery, characterization and use in D-arabitol and xylitol production by metabolically engineered Bacillus subtilis. Helsinki, Finland: University of Helsinki, Academic dissertation. Rafiqul ISM, Mimi Sakinah AM. 2012. A perspective bioproduction of xylitol by enzyme technology and future prospects. Int Food Res J 19: 405–408. Rao RS, Jyothi CP, Prakasham RS. 2006. Strain improvement of Candida tropicalis for the production of xylitol: biochemical and physiological characterization of wild-type and mutant strain CT-OMV5. J Microbiol 44:113–120. Rivas B, Torre P, Dominguez JM. 2003. Carbon material and bioenergetic balances of xylitol production from corncobs by Debaryomyces hansenii. Biotechnol Prog 19:706–713. Rivas B, Torre P, Dominguez JM, Converti A, Parajo´ JC. 2006. Purification of xylitol obtained by fermentation of corncob hydrolysates. J Agric Food Chem 54:4430–4435. Saha BC. 2003. Hemicellulose bioconversion. J Ind Microbiol Biotechnol 30:279–291.

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Sakakibara Y, Saha BC, Taylor P. 2009. Microbial production of xylitol from L-arabinose by metabolically engineered Escherichia coli. J Biosci Bioeng 107:506–511. Sampaio FC, da Silveira WB, Chaves-Alves VM, Coelho JLC. 2003. Screening of filamentous fungi for production of xylitol from D-xylose. Braz J Microbiol 34:325–328. Sasaki M, Jojima T, Inui M, Yukawa H. 2010. Xylitol production by recombinant Corynebacterium glutamicum under oxygen deprivation. Appl Microbiol Biotechnol 86:1057–1066. Saums WA, Schoen W. 1956. Preparation of high purity wood sugars. US patent 2759856. Sreenath HK, Chapman TW, Jeffries TW. 1986. Ethanol production from D-xylose in batch fermentations with Candida shehatae: process variables. Appl Microbiol Biotechnol 24:294–299. Sugiyama M, Suzuki S, Mihara Y, Hashiguchi K, Yokozeki K. 2001. Process for preparing xylitol. US patent 6303353 B1. Suzuki T, Yokoyama S, Kinoshita Y, Yamada H, Hatsu M, Takamizawa K, Kawai K. 1999. Expression of xyrA gene encoding for D-Xylose reductase of Candida tropicalis and production of xylitol in Escherichia coli. J Biosci Bioeng 87:280–284. Takeuchi S, Tonouchi N, Yokozeki K. 2001. Method for producing xylitol or D-xylulose in bacteria. US patent 6221634B1. Tapiainen T, Sormunen R, Kaijalainen T, Kontiokari T, Ika¨heimo I, Uhari M. 2003. Ultrastructure of Streptococcus pneumoniae after exposure to xylitol. J Antimicrob Chemother 54:225–228. Tran LH, Yogo M, Ojima H, Idota O, Kawai K, Suzuki T, Takamizawa K. 2004. The production of xylitol by enzymatic hydrolysis of agricultural wastes. Biotechnol Bioprocess Eng 9:223–228. Toivari MH, Ruohonen L, Miasnikov AN, Richard P, Penttila¨ M. 2007. Metabolic engineering of Saccharomyces cerevisiae for conversion of D-glucose to xylitol and other five-carbon sugars and sugar alcohols. Appl Environ Microbiol 73:5471–5476. Touster O. 1960. Essential pentosuria and the glucuronate-xylulose pathway. Fed Proc 19:977–983. Touster O. 1969. The uronic acid pathway and its defect in essential pentosuria. International Symposium on Metabolism, Physiology, and Clinical Use of Pentoses and Pentitols. Hakone, Japan:79–96. Touster O. 1974. The metabolism of polyols. In: Sipple HL, McNutt KW, editors. Sugars in nutrition. New York: Academic Press. p. 229–239. Touster O, Reynolds VH, Hutcheson RM. 1956. The reduction of l-xylulose to xylitol by uinea pig liver mitochondria. J Biol Chem 221: 697–709. Touster O, Shaw DR. 1962. Biochemistry of the acyclic polyols. Physiol Rev 42:181–225. Vandeska E, Kuzmanova S, Jeffries TW. 1995. Xylitol formation and key enzyme activities in Candida boidinii under different oxygen transfer rates. J Ferment Bioeng 80:513–516. Yahashi Y, Horitsu H, Kawai K, Suzuki T, Takamizawa K. 1996. Production of xylitol from D-xylose by Candida tropicalis: the effect of D-xylose feeding. J Ferm Technol 81:148–152. Ylikahri RH, Leino T. 1979. Metabolic interactions of xylitol and ethanol in healthy males. Metabolism 28:25–29. Yoon KY, Woodams EE, Hang YD. 2006. Enzymatic production of pentoses from the hemicellulose fraction of corn residues. Lebenson Wiss Technol 39:388–392. Yoshitake J, Ohiwa H, Shimamura M, Imai T. 1971. Production of polyalcohol by a Corynebacterium sp. Agric Biol Chem 35:905–911. Zhang J, Li S, Xu H, Zhou P, Zhang L, Ouyang P. 2013. Purification of xylitol dehydrogenase and improved production of xylitol by increasing XDH activity and NADH supply in Gluconobacter oxydans. J Agric Food Chem. [Online] Available at: http://www.ncbi.nlm.nih. gov/pubmed/?term¼PurificationþofþXylitolþDehydrogenaseþandþ ImprovedþProductionþofþXylitolþbyþIncreasingþXDHþActivity þandþNADHþSupplyþinþGluconobacterþoxydans. Accessed on 30 March 2013. Zhou P, Li S, Xu H, Feng X, Ouyang P. 2012. Construction and co-expression of plasmid encoding xylitol dehydrogenase and a cofactor regeneration enzyme for the production of xylitol from Darabitol. Enzyme Microb Technol 51:119–124.