# Chemoenzymatic synthesis of bacterial nonulosonic acids and glycans

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $309,114

## Abstract

Project Summary
Chemoenzymatic synthesis of bacterial nonulosonic acids and glycans
Sialic acids are a family of wide-spread nonulosonic acids (alpha-keto acids with a nine-carbon backbone) in
vertebrates and in some pathogenic bacteria. Bacteria also produce nonulosonic acids that have not been
found in animals. These bacterium-specific nonulosonic acids have been used by bacteria as part of their
capsular polysaccharides (CPSs) and lipopolysaccharides (LPSs) which are bacterial virulence factors and
potential vaccine candidates. Structurally defined bacterial CPSs, LPSs, and the corresponding
oligosaccharide repeating units are important probes to study their roles in bacterial infection and microbe-host
interaction including their influence on host immune systems. These carbohydrates are attractive synthetic
targets but pose significant synthetic challenges. In addition to bacterial specific nonulosonic acids, they may
contain other monosaccharide building blocks that have not been found in mammals. The glycosidic linkages
found in bacterial polysaccharides are also much more diverse than those in mammalian glycans. We propose
to develop efficient chemoenzymatic methods to synthesize bacterial nonulosonic acids and their glycans as
part of CPS and LPS oligosaccharides of pathogenic bacteria. These represent biologically important and
synthetically challenging targets. In the current proposal duration, the focus will be on bacterial glycans
containing legionaminic acid and their derivatives. Three specific aims are: 1, Synthesize acceptors and
monosaccharide chemoenzymatic synthons for one-pot multienzyme (OPME) glycosylation systems; 2,
Identify and characterize candidate sugar-1-P kinases, UDP-sugar synthetases, and glycosyltransferases; and
3, Chemoenzymatic synthesis of bacterial polysaccharide repeating units containing legionaminic acid or
derivatives. The enzymes identified and the monosaccharides designed are important tools and reagents for
accessing synthetic challenging carbohydrates and glycoconjugates that are not limited to the targets
described in the proposal. The oligosaccharides produced are essential probes for better understanding the
important roles of bacterial polysaccharides. They are also candidates for synthesizing structurally defined
carbohydrate-protein conjugate vaccines to combat bacterial infections.

## Key facts

- **NIH application ID:** 10186358
- **Project number:** 1R01GM141324-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Xi Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $309,114
- **Award type:** 1
- **Project period:** 2021-03-05 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186358

## Citation

> US National Institutes of Health, RePORTER application 10186358, Chemoenzymatic synthesis of bacterial nonulosonic acids and glycans (1R01GM141324-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10186358. Licensed CC0.

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