Use of a phosphonate methyltransferase in the identification of the fosfazinomycin biosynthetic gene cluster

Jiangtao Gao, Kou San Ju, Xiaomin Yu, Juan E. Velasquez, Subha Mukherjee, Jaeheon Lee, Changming Zhao, Bradley S. Evans, James R. Doroghazi, William W. Metcalf, Wilfred A. Van Der Donk

Research output: Contribution to journalArticle

Abstract

Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for stable isotope labeling of phosphonates in extract (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled Sadenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled.

Original languageEnglish (US)
Pages (from-to)1334-1337
Number of pages4
JournalAngewandte Chemie - International Edition
Volume53
Issue number5
DOIs
StatePublished - Jan 27 2014

Keywords

  • Antibiotics
  • Biosynthesis
  • Hydrazine
  • Natural products

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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