Abstract
GDP-mannose 3,5-epimerase (GM35E, GME) belongs to the short-chain dehydrogenase/reductase (SDR) protein superfamily and catalyses the conversion of GDP-d-mannose towards GDP-l-galactose. Although the overall reaction seems relatively simple (a double epimerization), the enzyme needs to orchestrate a complex set of chemical reactions, with no less than 6 catalysis steps (oxidation, 2x deprotonation, 2x protonation and reduction), to perform the double epimerization of GDP-mannose to GDP-l-galactose. The enzyme is involved in the biosynthesis of vitamin C in plants and lipopolysaccharide synthesis in bacteria. In this review, we provide a clear overview of these interesting epimerases, including the latest findings such as the recently characterized bacterial and thermostable GM35E representative and its mechanism revision but also focus on their industrial potential in rare sugar synthesis and glycorandomization.
Highlights
L-sugars have attracted scientific and industrial attention due to their importance as key constituents of biologically relevant molecules (Xia et al, 2014; Hélaine et al, 2015) [e.g., in antibiotics (Yu et al, 2013), bioactive oligosaccharides (Mulloy and Forster, 2000)] and potential for the pharmaceutical industry as building blocks for antiviral and anticancer drugs (Mathé and Gosselin, 2006)
98 (GDP-Man) aWT, or mutants in complex GDP-Man or GDP-L-Gal; N.R., not reported; N.D., not determined. bNative enzyme purified from A. thaliana. cRecombinant enzyme with N-terminal His-tag. dRecombinant enzyme with N-terminal glutathione-S-transferase tag
An L-Gul containing glycopeptide antibiotic with antitumor properties produced by Streptomyces verticillus (Du et al, 2000; Yu et al, 2013) for which the sugar moiety has been shown to stimulates the uptake of this drug by cancer cells (Schroeder et al, 2014)
Summary
L-sugars have attracted scientific and industrial attention due to their importance as key constituents of biologically relevant molecules (Xia et al, 2014; Hélaine et al, 2015) [e.g., in antibiotics (Yu et al, 2013), bioactive oligosaccharides (Mulloy and Forster, 2000)] and potential for the pharmaceutical industry as building blocks for antiviral and anticancer drugs (i.e., nucleosides analogues) (Mathé and Gosselin, 2006). An example of the latter is lamivudine ( known as 3TC), an L-nucleoside analogue that is used as antiretroviral medication to prevent and treat HIV/AIDS and treat chronic hepatitis B (Gumina et al, 2001).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
