MoeH5: a natural glycorandomizer from the moenomycin biosynthetic pathway.

Abstract

The biosynthesis of the phosphoglycolipid antibiotic moenomycin A attracts the attention of researchers hoping to develop new moenomycin-based antibiotics against multidrug resistant Gram-positive infections. There is detailed understanding of most steps of this biosynthetic pathway in Streptomyces ghanaensis (ATCC14672), except for the ultimate stage, where a single pentasaccharide intermediate is converted into a set of unusually modified final products. Here we report that only one gene, moeH5, encoding a homologue of the glutamine amidotransferase (GAT) enzyme superfamily, is responsible for the observed diversity of terminally decorated moenomycins. Genetic and biochemical evidence support the idea that MoeH5 is a novel member of the GAT superfamily, whose homologues are involved in the synthesis of various secondary metabolites as well as K and O antigens of bacterial lipopolysaccharide. Our results provide insights into the mechanism of MoeH5 and its counterparts, and give us a new tool for the diversification of phosphoglycolipid antibiotics.

• Authors: Bohdan Ostash, Jennifer Campbell, Andriy Luzhetskyy, Suzanne Walker
• Journal: Molecular microbiology (Mol Microbiol) Vol. 90 Issue 6 Pg. 1324-38 (Dec 2013) ISSN: 1365-2958 [Electronic] England
• PMID: 24164498 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Anti-Bacterial Agents
• Bacterial Proteins
• Bambermycins

Topics

• Anti-Bacterial Agents (biosynthesis)
• Bacterial Proteins (genetics, metabolism)
• Bambermycins (biosynthesis)
• Biosynthetic Pathways
• Gene Expression Regulation, Bacterial
• Gene Knockout Techniques
• Genes, Bacterial
• Multigene Family
• Phylogeny
• Secondary Metabolism
• Sequence Homology, Amino Acid
• Streptomyces (enzymology, genetics)