Genome mining and metabolomics uncover a rare D-capreomycidine containing natural product and its biosynthetic gene cluster

Neil L. Kelleher, Regan J. Thomson, James H. Tryon, Jennifer C. Rote, Li Chen, Matthew T. Robey, Marvin M. Vega, Wan Cheng Phua, William W. Metcalf, Kou San Ju

Research output: Contribution to journalArticlepeer-review

Abstract

We report the metabolomics-driven genome mining of a new cyclic-guanidino incorporating non-ribosomal peptide synthetase (NRPS) gene cluster and full structure elucidation of its associated hexapeptide product, faulknamycin. Structural studies unveiled that this natural product contained the previously unknown (R,S)-stereoisomer of capreomycidine, D-capreomycidine. Furthermore, heterologous expression of the identified gene cluster successfully reproduces faulknamycin production without an observed homologue of VioD, the pyridoxal phosphate (PLP)dependent enzyme found in all previous L-capreomycidine biosynthesis. An alternative NRPS-dependent pathway for D-capreomycidine biosynthesis is proposed.

Original languageEnglish (US)
Pages (from-to)3013-3020
Number of pages8
JournalACS chemical biology
Volume15
Issue number11
DOIs
StatePublished - Nov 20 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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