Nocardiopsistins A-C: New angucyclines with anti-MRSA activity isolated from a marine sponge-derived Nocardiopsis sp. HB-J378

Dongbo Xu, Keshav K. Nepal, Jing Chen, Dedra Harmody, Haining Zhu, Peter J. McCarthy, Amy E. Wright, Guojun Wang

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Marine natural products have become an increasingly important source of new drug leads during recent years. In an attempt to identify novel anti-microbial natural products by bioprospecting deep-sea Actinobacteria, three new angucyclines, nocardiopsistins A-C, were isolated from Nocardiopsis sp. strain HB-J378. Notably, the supplementation of the rare earth salt Lanthanum chloride (LaCl3) during fermentation of HB-J378 significantly increased the yield of these angucyclines. The structures of nocardiopsistins A-C were identified by 1D and 2D NMR and HR-MS data. Nocardiopsistins A-C have activity against MRSA (methicillin-resistant Staphylococcus aureus) with MICs of 3.12–12.5 μg/mL; the potency of nocardiopsistin B is similar to that of the positive control, chloramphenicol. Bioinformatic analysis of the draft genome of HB-J378 identified a set of three core genes in a biosynthetic gene cluster that encode a typical aromatic or type II polyketide synthase (PKS) system, including ketoacyl:ACP synthase α-subunit (KSα), β-subunit (KSβ) and acyl carrier protein (ACP). The production of nocardiopsistins A-C was abolished when the three genes were knocked out, indicating their indispensable role in the production of nocardiopsistins.

Original languageEnglish (US)
Pages (from-to)246-251
Number of pages6
JournalSynthetic and Systems Biotechnology
Volume3
Issue number4
DOIs
StatePublished - Dec 2018
Externally publishedYes

Keywords

  • Actinobacteria
  • Angucycline
  • Anti-MRSA
  • LaCl
  • Nocardiopsis
  • Nocardiopsistins

ASJC Scopus subject areas

  • Structural Biology
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Genetics

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