Enzymes for the biocatalytic production of rare sugars

Beerens, Koen; Desmet, Tom; Soetaert, Wim

doi:10.1007/s10295-012-1089-x

Cited by 168 publications

(112 citation statements)

References 130 publications

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“…The use of inexpensive raw substrates for the production of rare sugars is now attracting considerable attention. Previous studies confirmed the validity of this approach; for example, L-xylulose, D-tagatose, D-sorbose, Dpsicose, D-talitol, and allitol were successfully produced using microorganisms [7][8][9][10][11]. Among these, allitol is a rare hexitol that is synthesised by the reduction of D-psicose [12].…”

Section: Introductionmentioning

confidence: 63%

Synthesis of allitol from D-psicose using ribitol dehydrogenase and formate dehydrogenase

Hassanin¹,

Letsididi²,

Koko³

et al. 2017

Trop. J. Pharm Res

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Section: Introductionmentioning

confidence: 63%

Synthesis of allitol from D-psicose using ribitol dehydrogenase and formate dehydrogenase

Hassanin¹,

Letsididi²,

Koko³

et al. 2017

Trop. J. Pharm Res

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“…L-Sugars, which are one large group of rare sugars, often hold enormous potential for applications in the pharmaceutical industry (9)(10)(11). For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12,13).…”

Section: Dhap-dependent Aldolases Create Two New Stereogenic Centers mentioning

confidence: 99%

“…For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12,13). L-Sorbose has been applied to produce the potent glycosidase inhibitor 1-deoxygalactonojirimycin and L-ascorbic acid, known as vitamin C (11,14). Several (bio)chemical methods have been applied to synthesize L-sugars because of their low nat-ural abundance.…”

Section: Dhap-dependent Aldolases Create Two New Stereogenic Centers mentioning

confidence: 99%

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

Yang

Men

et al. 2015

Appl Environ Microbiol

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The property of loose stereochemical control at aldol products from aldolases helped to synthesize multiple polyhydroxylated compounds with nonnatural stereoconfiguration. In this study, we discovered for the first time that some fructose 1,6-diphosphate aldolases (FruA) and tagatose 1,6-diphosphate (TagA) aldolases lost their strict stereoselectivity when using L-glyceraldehyde and synthesized not only L-sorbose but also a high proportion of L-psicose. Among the aldolases tested, TagA A ldolases are remarkably useful and have been widely investigated for catalyzed COC bond formation (1). The ability to catalyze aldol addition reactions from small chiral polyfunctional molecules and generate up to two new stereogenic centers allows aldolases to synthesize a broad range of both natural and novel polyhydroxylated compounds. Among the aldolase families, dihydroxyacetone-phosphate (DHAP)-dependent aldolases, which utilize DHAP as the donor substrate and accept a broad range of acceptor aldehydes, are widely investigated. Well-known members of this class include fuculose 1-phosphate aldolase (FucA), rhamnulose 1-phosphate aldolase (RhaD), fructose 1,6-diphosphate aldolase (FruA), and tagatose 1,6-diphosphate aldolase (TagA) (2). These enzymes have been used to synthesize several new deoxy or phosphorylated sugars and iminocyclitols (3-5). DHAP-dependent aldolases create two new stereogenic centers at C atoms 3 and 4 ([3S,4R], [3S,4S], [3R,4S], [3R,4R]). FucA, FruA, RhaD, and TagA generally form (3R,4R), (3S,4R), (3R,4S), and (3S,4S) stereoconfigurations, respectively (1, 2). However, some aldolases sometimes lost their strict stereoselectivity at the C-4 stereocenter with some aldehydes as substrates. For example, RhaD aldolase from Escherichia coli catalyzed DHAP and L-glyceraldehyde to form L-fructose (3R,4S). However, D-sorbose (3R,4S) and D-psicose (3R,4R) were formed when using D-glyceraldehyde (6-8). Moreover, FucA aldolase from E. coli catalyzed DHAP and L-glyceraldehyde to form the single product L-tagatose (3R,4R). However, FucA from Thermus thermophilus HB8 generated L-tagatose (3R,4R) and L-fructose (3R,4S) simultaneously from the same substrates. This finding indicated that aldolases had a high level of stereocontrol at C-3; however, the configuration of the stereocenter at C-4 in some cases depended on the particular enzyme and acceptor structure. This aldolase property can be well utilized to synthesize various types of rare sugars. Thus far, no reports have shown this property for FruA aldolase. In addition, TagA aldolases form diastereomer mixtures of product, in which instead of the natural configuration (3S,4S), those of the configuration (3S,4R) predominated (Ͼ90%) (4).L-Sugars, which are one large group of rare sugars, often hold enormous potential for applications in the pharmaceutical industry (9-11). For example, several L-sugars can be used to produce L-nucleoside analogues, which showed increased antiviral activity, better metabolic stability, and more favorable toxicological profiles (12, 1...

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“…It constitutes the central enzyme for biocatalytic access to rare monosaccharides, which have recently attracted great interest as low calorie sweeteners, chiral building blocks or as active pharmaceutical ingredients [7] . By combining DTE with maximally two additional isomerases, the whole set of 24 hexoses can be generated in a short cascade reaction from only 4 starting materials that are cheaply available (D-glucose, D-fructose, D-galactose, L-sorbose) [8] .…”

Section: Introductionmentioning

confidence: 99%

Directed Divergent Evolution of a Thermostable D‐Tagatose Epimerase towards Improved Activity for Two Hexose Substrates

et al. 2015

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Abstract:We exploit the functional promiscuity of an engineered thermostable variant of a promiscuous D-tagatose epimerase (DTE Var8) to morph it into two efficient catalysts for the C3 epimerization of D-fructose to D-psicose and of L-sorbose to L-tagatose. Iterative single-site randomization and screening of 48 residues in the first and second shell around the substrate binding site of Var8 yielded 8-sites mutant IDF8 with an 9-fold improved kcat for the epimerization of D-fructose, and the 6-sites mutant ILS6 with an 14-fold improved epimerization of L-sorbose compared to Var8. Structure analysis of IDF8 revealed a charged patch at the entrance of its active site that supposedly facilitates the entry of the polar substrate, whereas the improvement in variant ILS6 is thought to relate to subtle changes in the hydration of the bound substrate. The structures will inform future engineering efforts of these and other isomerizing enzymes for the production of rare.

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Enzymes for the biocatalytic production of rare sugars

Cited by 168 publications

References 130 publications

Synthesis of allitol from D-psicose using ribitol dehydrogenase and formate dehydrogenase

Synthesis of allitol from D-psicose using ribitol dehydrogenase and formate dehydrogenase

Biosynthesis of l -Sorbose and l -Psicose Based on C—C Bond Formation Catalyzed by Aldolases in an Engineered Corynebacterium glutamicum Strain

Directed Divergent Evolution of a Thermostable D‐Tagatose Epimerase towards Improved Activity for Two Hexose Substrates

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