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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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

  • Molecular Medicine
  • Biochemistry

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