An Overview of Sugar Nucleotide-Dependent Glycosyltransferases for Human Milk Oligosaccharide Synthesis

Abstract

Human milk oligosaccharides (HMOs) have received increasing attention because of their special effects on infant health and commercial value as the new generation of core components in infant formula. Currently, large-scale production of HMOs is generally based on microbial synthesis using metabolically engineered cell factories. Introduction of the specific glycosyltransferases is essential for the construction of HMO-producing engineered strains in which the HMO-producing glycosyltransferases are generally sugar nucleotide-dependent. Four types of glycosyltransferases have been used for typical glycosylation reactions to synthesize HMOs. Soluble expression, substrate specificity, and regioselectivity are common concerns of these glycosyltransferases in practical applications. Screening of specific glycosyltransferases is an important research topic to solve these problems. Molecular modification has also been performed to enhance the catalytic activity of various HMO-producing glycosyltransferases and to improve the substrate specificity and regioselectivity. In this article, various sugar nucleotide-dependent glycosyltransferases for HMO synthesis were overviewed, common concerns of these glycosyltransferases were described, and the future perspectives of glycosyltransferase-related studies were provided.

Characterization of a GH20 β-N-Acetylhexosaminidase from Flavobacterium algicola Suitable to Synthesize Lacto-N-triose II

“…The whole-cell synthesis methods have been improved to obtain the expected molecules with medium to good efficiency because of the advances in synthetic biology and systems biology tools, particularly molecular biology tools and metabolic pathway assembly . Currently, the commercial production of LNT2 is generally based on the whole-cell synthesis method . This method introduces the genes involved in the synthesis of donor sugar nucleotides and the corresponding heterologous glycosyltransferase genes into microorganisms to synthesize LNT2 by microbial metabolic engineering.…”