Alg mannosyltransferases: From functional and structural analyses to the lipid-linked oligosaccharide pathway reconstitution

Biochim Biophys Acta Gen Subj. 2022 May;1866(5):130112. doi: 10.1016/j.bbagen.2022.130112. Epub 2022 Feb 22.

Abstract

Background: N-glycosylation is initiated from the biosynthesis of lipid-linked oligosaccharide (LLO) on the endoplasmic reticulum (ER), which is catalyzed by a series of Alg (asparagine-linked glycosylation) proteins.

Scope of review: This review summarizes our recent studies on the enzymology of Alg mannosyltransferases (MTases). We also discuss the membrane topology and physiological importance of several ER cytosolic Alg proteins.

Major conclusions: Utilizing an efficient prokaryotic protein expression system and a new LC-MS quantitative activity assay, we overexpressed all Alg MTases and performed enzymology studies. Moreover, by reconstituting the LLO pathway, the high-yield chemoenzymatic synthesis of high-mannose-type N-glycans was accomplished using recombinant Alg MTases.

General significance: The analysis of the enzymology and topology of Alg MTases has provided valuable biochemical information in the LLO biosynthesis pathway. In addition, an efficient chemoenzymatic strategy that could prepare various oligomannose-type N-glycans in sufficient amounts was established for further biological assays.

Keywords: Alg mannosyltransferase; Chemoenzymatic synthesis; Lipid-linked oligosaccharide; N-glycosylation; Quantitative assay.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Endoplasmic Reticulum / metabolism
  • Lipopolysaccharides
  • Mannosyltransferases* / metabolism
  • Oligosaccharides / metabolism
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Lipopolysaccharides
  • Oligosaccharides
  • lipid-linked oligosaccharides
  • Mannosyltransferases