Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools. (February 2021)

• Record Type: Journal Article
• Authors: Cioce, Anna; Malaker, Stacy A.; Schumann, Benjamin
• Is Part Of: Current opinion in chemical biology. Volume 60(2021)
• Page Start: 66
• Page End: 78
• Publication Date: 2021-02
• Subjects: Glycosylation -- Bioorthogonal -- Glycosyltransferase -- Mucin -- Glycoprotein -- Protein engineering -- Click chemistry; Bioorganic chemistry -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Clinical biochemistry -- Periodicals; Biochemistry -- Periodicals; Chimie bio-organique -- Périodiques; Biologie -- Périodiques; 572.05
• DOI: 10.1016/j.cbpa.2020.09.001
• Languages: English
• ISSNs: 1367-5931

Abstract

Abstract: Protein glycosylation fundamentally impacts biological processes. Nontemplated biosynthesis introduces unparalleled complexity into glycans that needs tools to understand their roles in physiology. The era of quantitative biology is a great opportunity to unravel these roles, especially by mass spectrometry glycoproteomics. However, with high sensitivity come stringent requirements on tool specificity. Bioorthogonal metabolic labeling reagents have been fundamental to studying the cell surface glycoproteome but typically enter a range of different glycans and are thus of limited specificity. Here, we discuss the generation of metabolic 'precision tools' to study particular subtypes of the glycome. A chemical biology tactic termed bump-and-hole engineering generates mutant glycosyltransferases that specifically accommodate bioorthogonal monosaccharides as an enabling technique of glycobiology. We review the groundbreaking discoveries that have led to applying the tactic in the living cell and the implications in the context of current developments in mass spectrometry glycoproteomics.