Structure-function relationships in NDP-sugar active SDR enzymes: Fingerprints for functional annotation and enzyme engineering.

Short-chain Dehydrogenase/Reductase enzymes that are active on nucleotide sugars (abbreviated as NS-SDR) are of paramount importance in the biosynthesis of rare sugars and glycosides. Some family members have already been extensively characterized due to their direct implication in metabolic disorders or in the biosynthesis of virulence factors. In this review, we combine the knowledge gathered from studies that typically focused only on one NS-SDR activity with an in-depth analysis and overview of all of the different NS-SDR families (169,076 enzyme sequences).

Expanding the Enzyme Repertoire for Sugar Nucleotide Epimerization: The CDP-Tyvelose 2-Epimerase from for Glucose/Mannose Interconversion.

Epimerization of sugar nucleotides is central to the structural diversification of monosaccharide building blocks for cellular biosynthesis. Epimerase applicability to carbohydrate synthesis can be limited, however, by the high degree of substrate specificity exhibited by most sugar nucleotide epimerases. Here, we discovered a promiscuous type of CDP-tyvelose 2-epimerase (TyvE)-like enzyme that promotes C2-epimerization in all nucleotide (CDP, UDP, GDP, ADP, TDP)-activated forms of d-glucose.

GDP-altrose as novel product of GDP-mannose 3,5-epimerase: Revisiting its reaction mechanism.

GDP-mannose 3,5-epimerase (GM35E) catalyzes the double epimerization of GDP-mannose to yield GDP-l-galactose. GDP-l-gulose (C5-epimer) has previously been detected as a byproduct of this reaction, indicating that C3,5-epimerization occurs through an initial epimerization at C5. Given these products, GM35E constitutes a valuable bridge between d- and l-hexoses.

Determinants of the Nucleotide Specificity in the Carbohydrate Epimerase Family 1.

In recent years, carbohydrate epimerases have attracted increasing attention as promising biocatalysts for the production of specialty sugars and derivatives. The vast majority of these enzymes are active on nucleotide-activated sugars, rather than on their free counterparts. Although such epimerases are known to have a clear preference for a particular nucleotide (UDP, GDP, CDP, or ADP), very little is known about the determinants of the respective specificities.

Characterization of the First Bacterial and Thermostable GDP-Mannose 3,5-Epimerase.

GDP-mannose 3,5-epimerase (GM35E) catalyzes the conversion of GDP-mannose towards GDP-l-galactose and GDP-l-gulose. Although this reaction represents one of the few enzymatic routes towards the production of l-sugars and derivatives, it has not yet been exploited for that purpose. One of the reasons is that so far only GM35Es from plants have been characterized, yielding biocatalysts that are relatively unstable and difficult to express heterologously.

Converting Galactose into the Rare Sugar Talose with Cellobiose 2-Epimerase as Biocatalyst.

Cellobiose 2-epimerase from (CE) reversibly converts a glucose residue to a mannose residue at the reducing end of β-1,4-linked oligosaccharides. In this study, the monosaccharide specificity of CE has been mapped and the synthesis of d-talose from d-galactose was discovered, a reaction not yet known to occur in nature. Moreover, the conversion is industrially relevant, as talose and its derivatives have been reported to possess important antimicrobial and anti-inflammatory properties.

A structural classification of carbohydrate epimerases: From mechanistic insights to practical applications.

In recent years, carbohydrate epimerases have attracted a lot of attention as efficient biocatalysts that can convert abundant sugars (e.g.d-fructose) directly into rare counterparts (e.