Issue 8, 2016

New insights into the biosynthesis of fosfazinomycin

Abstract

The biosynthetic origin of a unique hydrazide moiety in the phosphonate natural product fosfazinomycin is unknown. This study presents the activities of five proteins encoded in its gene cluster. The flavin-dependent oxygenase FzmM catalyses the oxidation of L-Asp to N-hydroxy-Asp. When FzmL is added, fumarate is produced in addition to nitrous acid. The adenylosuccinate lyase homolog FzmR eliminates acetylhydrazine from N-acetyl-hydrazinosuccinate, which in turn is the product of FzmQ-catalysed acetylation of hydrazinosuccinate. Collectively, these findings suggest a path to N-acetylhydrazine from L-Asp. The incorporation of nitrogen from L-Asp into fosfazinomycin was confirmed by isotope labelling studies. Installation of the N-terminal Val of fosfazinomycin is catalysed by FzmI in a Val-tRNA dependent process.

Graphical abstract: New insights into the biosynthesis of fosfazinomycin

Supplementary files

Article information

Article type
Edge Article
Submitted
29 Mar 2016
Accepted
22 Apr 2016
First published
06 May 2016
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2016,7, 5219-5223

Author version available

New insights into the biosynthesis of fosfazinomycin

Z. Huang, K. A. Wang and W. A. van der Donk, Chem. Sci., 2016, 7, 5219 DOI: 10.1039/C6SC01389A

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