Monosaccharides and their derivatives are referred to as rare sugars. Monosaccharides have applications in nutrition and pharmaceutical industries and they are used as precursors for drug candidates and natural products. The availability of these rare sugars is restricted and the enzymatic and microbial transformations have become vital tools to synthesize these rare sugars. According to a study, the importance of rare sugars and the nucleosides derived from these sugars, has increased dramatically as these molecules are mostly used in preparations of antiviral and anticancer drugs.
This article discusses the biosynthesis of some of the rare hexoses and sugar alcohols like L-fructose, L-glucose, L-galactose, Allitol, and L-Sorbitol. To improve the rare sugar production, procedures that increase the catalytic efficiency or selectivity of substrate by the related enzymes are practiced in some research studies that are reviewed here.
Biosynthesis of rare ketohexose, L-Fructose
L-fructose is observed as an inhibitor of glycosidases. Initially in a study, L-fructose was synthesized using L-mannose as substrate through aldo-keto isomerization. Oxidation of L-mannose by bacteria also results in L-fructose formation. The enzyme DTEase (D-tagose 3-epimerase family) of Pseudomonas sp. ST-24 catalyzes the epimerization of L-psicose to generate 56 percent of L-fructose. In another method reported in yet another study, DHAP or dihydroxyacetone phosphate dependent aldolase called L-rhamnulose-1 phosphate aldolase, could make use of L-glyceradehyde as substrate to produce 55 percent of L-fructose by using DHAP as another substrate. In another study, L-rhamnulose-1 phosphate aldolase could use DHA as substrate instead of DHAP and borate buffer in the above reaction. Depending on the reaction method mentioned above, one step L-fructose synthesis was achieved practically from DHA and glyceraldehyde and the yield of the synthesis was about 92 percent. Optimization of synthesis can be done in the laboratory which reduces the cost and optimizes the best possible average yield.
Biosynthesis of rare aldohexose, L-glucose
L-glucose is an inhibitor of bacterial growth and glucosidases and it does not naturally occur in higher organisms. L-glucose acts as a precursor for the synthesis of glycoconjugate vaccines that are active against Shigella sonne, an enteropathogenic bacterium. Isomerization of L-fructose in Candida utilis catalyzed by D-xylose isomerase yields L-glucose. According to a study, L-glucose also results from isomerization of L-fructose in Klebsiella pneumonia mutant strain with the help of catalyzing enzyme D-arabinose isomerase. According to the above study, 35 percent of L-glucose was yielded through mutant strain. The galactose oxidase and catalase were immobilized on solid supports like crab shell particles or Ocimum sanctum seeds and were tested for their involvement in L-glucose production from D-sorbitol. Catalase acts as destroyer of the byproduct hydrogen peroxide and enhances the L-glucose formation. The blockage of the galactose oxidase activity by hydrogen peroxide is removed by catalase.
L-galactose is the precursor for the synthesis of L-ascorbate. An important study on L-galactose synthesis reported that there are two steps for synthesizing L-galactose on large scale from L-Sorbose. First step involves conversion of L-Sorbose by DTEase of mutant Pseusomonas sps. ST24 into L-galactose. In the second step, L-galactose results from L-Sorbose by the action of recombinant L-rhamnose isomerase of E.coli JM109. In another strategy of L-galactose formation, L-Sorbose was first epimerized at 3rd carbon by DTEase to yield 28 percent of L-tagatose which existed in equilibrium with 30 percent of L-galactose formed by the catalysis of L-rhamnose isomerase.
Direct synthesis of L-galactose occurred by the oxidization of galactitol catalyzed by D-galactose oxidase as well as immobilized galactose oxidase, which might give rise to low levels of L-galactose. The oxidation of galactitol into L-galactose can be done in large scale by the cells of E.coli consisting of mannitol dehydrogenase.
Epimerization of D-glucose helps in the biosynthesis of L-galactose. The epimerization is done through another novel metabolic pathway emerging from the biosynthesis of L-galactan by triple epimerization of 2nd, 3rd and 5th carbons. Triple epimerization is known to bring about inversion of the configurations of 2nd, 3rd and 5th carbons.
Biosynthesis of rare sugar alcohol, Allitol
Sugar alcohols are obtained from hexoses and pentoses. They are carbohydrates in the hydrogenated form in which the carbonyl group is reduced.
Aliitol synthesis occurs by reducing or hydrogenating D-psicose sugar, which results from the conversion of D-fructose into D-psicose by the enzyme DTEase. As the conversion rate of D-psicose and its concentration are noticeably low for the bacteria to reduce it, three enzymes like ribitol dehydrogenase, DTEase and formate dehydrogenase are used. The NADH that is required for the conversion of psicose into allitol is obtained by the formate dehydrogenase reaction which promotes the formation of allitol.
The cells of Aureobasidium pullulans strain LP23 act as catalysts for the conversion of L-fructose into L-Sorbitol. The catalysis of L-Sorbitol formation is also observed to be triggered by L-arabinose. The addition of erythritol to the reaction mixture increased the formation of L-Sorbitol, possibly due to the erythritol dehydrogenation generating NADH useful in L-Sorbitol synthesis.
The latest developments in bio-engineering and genomics aid in improving the enzymatic properties or in generating novel and robust bio-catalysts for industrial level of production.
Zijie Li, Yahui Gao, Hideki Nakanishi, Xiaodong Gao and Li Cai. Biosynthesis of rare hexoses using microorganisms and related enzymes. Beilstein J. Org. Chem. 2013, 9, 2434-2445. http://ebookbrowsee.net/1860-5397-9-281-pdf-d620274984.
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