Total biosynthesis of legionaminic acid, a bacterial sialic acid analogue

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DOIResolve DOI: http://doi.org/10.1002/anie.201606006
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TypeArticle
Journal titleAngewandte Chemie International Edition
ISSN1433-7851
Volume55
Issue39
Pages1201812021
AbstractLegionaminic acid, Leg5,7Ac2, a nonulosonic acid like 5-acetamido neuraminic acid (Neu5Ac, sialic acid), is found in cell surface glycoconjugates of bacteria including the pathogens Campylobacter jejuni, Acinetobacter baumanii and Legionella pneumophila. The presence of Leg5,7Ac2 has been correlated with virulence in humans by mechanisms that likely involve subversion of the host's immune system or interactions with host cell surfaces due to its similarity to Neu5Ac. Investigation into its role in bacterial physiology and pathogenicity is limited as there are no effective sources of it. Herein, we construct a de novo Leg5,7Ac2 biosynthetic pathway by combining multiple metabolic modules from three different microbial sources (Saccharomyces cerevisiae, C. jejuni, and L. pneumophila). Over-expression of this de novo pathway in Escherichia coli that has been engineered to lack two native catabolic pathways, enables significant quantities of Leg5,7Ac2 (≈120 mg L−1 of culture broth) to be produced. Pure Leg5,7Ac2 could be isolated and converted into CMP-activated sugar for biochemical applications and a phenyl thioglycoside for chemical synthesis applications. This first total biosynthesis provides an essential source of Leg5,7Ac2 enabling study of its role in prokaryotic and eukaryotic glycobiology.
Publication date
PublisherWiley
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NRC numberNRC-HHT-53320
NPARC number23001896
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Record identifiera7bc358a-f8a6-4eda-a128-8b36c4e5a254
Record created2017-05-09
Record modified2017-05-15
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