Premium
Total Biosynthesis of Legionaminic Acid, a Bacterial Sialic Acid Analogue
Author(s) -
Hassan Mohamed I.,
Lundgren Benjamin R.,
Chaumun Michael,
Whitfield Dennis M.,
Clark Brady,
Schoenhofen Ian C.,
Boddy Christopher N.
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201606006
Subject(s) - glycobiology , campylobacter jejuni , legionella pneumophila , microbiology and biotechnology , biochemistry , sialic acid , escherichia coli , biology , biosynthesis , bacteria , bacterial cell structure , neuraminic acid , glycoconjugate , virulence , glycan , chemistry , enzyme , glycoprotein , gene , genetics
Legionaminic acid, Leg5,7Ac 2 , 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 Leg5,7Ac 2 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 Leg5,7Ac 2 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 Leg5,7Ac 2 (≈120 mg L −1 of culture broth) to be produced. Pure Leg5,7Ac 2 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 Leg5,7Ac 2 enabling study of its role in prokaryotic and eukaryotic glycobiology.