New insights into the biosynthesis of fosfazinomycin

Zedu Huang, Kwo Kwang Abraham Wang, Wilfred A. Van Der Donk

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)5219-5223
Number of pages5
JournalChemical Science
Issue number8
StatePublished - 2016

ASJC Scopus subject areas

  • General Chemistry


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