Bacterial sialyltransferases and their use in biocatalytic cascades for sialo-oligosaccharide production

Sabine Schelch, Chao Zhong, Barbara Petschacher, Bernd Nidetzky*

*Corresponding author for this work

Research output: Contribution to journalReview article

Abstract

Sialic acids are important recognition sites in protein- and lipid-linked glycans of higher organisms and of select bacteria and protozoa. They are also prominent in human milk oligosaccharides. Defined sialo-oligosaccharides have interesting applications in chemical glycobiology and represent emerging ingredients for health-related nutrition. The growing demand for sialo-oligosaccharides has promoted developments in multidisciplinary carbohydrate synthesis, with approaches by cascade bio-catalysis having a leading role. The key synthetic step involves catalysis by sialyltransferases (EC 2.4.99.-) and consists in attaching sialic acid from a cytidine 5′-monophosphate-activated donor (CMP-sialic acid) to the nascent oligosaccharide acceptor. Sialyltransferases from bacteria, in general, show convenient properties for application (e.g., relative ease of recombinant production; high specific activity and operational stability). Here, we review salient characteristics of the bacterial sialyltransferases active on D-galactose- and N-acetyl-D-galactosamine-containing acceptors and highlight advances of their development into efficient biocatalysts. We also show integration of these sialyltransferases into multistep enzymatic cascades for sialo-oligosaccharide (e.g., sialyllactose) production from expedient substrates, using in situ formation of the CMP-sialic acid donor. We summarize functional parameters of the enzymes for CMP-sialic acid supply and analyze multi-enzymatic synthesis of sialo-oligosaccharides from a reaction engineering point of view. We discuss opportunities of sialyltransferase cascades for efficient sialo-oligosaccharide production in vitro and in vivo.

Original languageEnglish
Article number107613
JournalBiotechnology Advances
Volume44
DOIs
Publication statusPublished - 15 Nov 2020

Keywords

  • CMP-sialic acid regeneration
  • Neuraminic acid
  • One-pot multi-enzyme cascade
  • Reaction engineering
  • Sialic acid
  • Sialo-oligosaccharide
  • Sialyltransferase

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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