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Isolation and structure elucidation of lipopeptide antibiotic taromycin B from the activated taromycin biosynthetic gene cluster.

Authors
  • Reynolds, Kirk A1, 2
  • Luhavaya, Hanna1
  • Li, Jie1
  • Dahesh, Samira3
  • Nizet, Victor3, 4
  • Yamanaka, Kazuya1
  • Moore, Bradley S1, 4
  • 1 Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA, USA.
  • 2 Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA, USA.
  • 3 Department of Pediatrics, University of California at San Diego, La Jolla, CA, USA.
  • 4 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, La Jolla, CA, USA.
Type
Published Article
Journal
The Journal of antibiotics
Publication Date
Feb 01, 2018
Volume
71
Issue
2
Pages
333–338
Identifiers
DOI: 10.1038/ja.2017.146
PMID: 29184121
Source
Medline
License
Unknown

Abstract

In the ongoing effort to unlock the chemical potential of marine bacteria, genetic engineering of biosynthetic gene clusters (BGCs) is increasingly used to awake or improve expression of biosynthetic genes that may lead to discovery of novel bioactive natural products. Previously, we reported the successful capture, engineering and heterologous expression of an orphan BGC from the marine actinomycete Saccharomonospora sp. CNQ-490, which resulted in the isolation of the novel lipopeptide antibiotic taromycin A. Herein we report the isolation and structure elucidation of taromycin B, the second most abundant product of the taromycin biosynthetic series, and show that taromycins A and B exhibit complex chromatographic properties indicative of interconverting conformations. Taromycins A and B display potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium clinical isolates, suggestive that the taromycin molecular scaffold is a promising starting point for further derivatization to produce compounds with promising antibiotic characteristics.

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