Biological strategies for oligo/polysaccharide synthesis: biocatalyst and microbial cell factory

Liting Zhao^a,b, Zhongbao Ma^a,b, Jian Yin^a, Guiyang Shi^a,b,c, Zhongyang Ding^a,b,c

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, China.

Abstract

Oligosaccharides and polysaccharides constitute the principal components of carbohydrates, which are important biomacromolecules that demonstrate considerable bioactivities. However, the variety and structural complexity of oligo/polysaccharides represent a major challenge for biological and structural explorations. To access structurally defined oligo/polysaccharides, biological strategies using glycoenzyme biocatalysts have shown remarkable synthetic potential attributed to their regioselectivity and stereoselectivity that allow mild, structurally controlled reaction without addition of protecting groups necessary in chemical strategies. This review summarizes recent biotechnological approaches of oligo/polysaccharide synthesis, which mainly includes in vitro enzymatic synthesis and cell factory synthesis. We have discussed the important factors involved in the production of nucleotide sugars. Furthermore, the strategies established in the cell factory and enzymatic syntheses are summarized, and we have highlighted concepts like metabolic flux rebuilding and regulation, enzyme engineering, and route design as important strategies. The research challenges and prospects are also outlined and discussed.

Keywords: oligo/polysaccharide, nucleotide sugar, bio-based strategy, enzymatic catalysis, cell factory.