Discovery of the Lipopeptides Albubactins A-H from Streptomyces albidoflavus RKJM0023 via Chemical Elicitation with Rhamnolipids and Synthesis of Albubactin A

J Nat Prod. 2024 Jul 26;87(7):1682-1693. doi: 10.1021/acs.jnatprod.3c01234. Epub 2024 Jun 28.

Abstract

The marine tunicate-derived Streptomyces albidoflavus RKJM0023 was cultured in the presence of a rhamnolipid mixture in an effort to elicit the production of silent natural products. MS/MS-based molecular networking analysis enhanced with nonparametric statistics highlighted the upregulation of a molecular cluster (Kruskal-Wallis p = 1.6 e-6 for 1) in which no MS/MS features had library matches. Targeted isolation of these features resulted in the discovery of nine new N-acylated lipopeptides, albubactins A-H (1-8) each containing a unique glutamine tripeptide and a C-terminal ethyl ester moiety. Three related albubactin acids A-C (9-11) lacking the ethyl ester were also identified. NMR spectroscopy and UPLC-HR-ESI-MS/MS demonstrated that the albubactins were obtained as mixtures that shared a common m/z and differed only in their acylated terminal groups. Due to the complex spectroscopic elucidation with many overlapping shifts, a total synthesis of albubactin A (1) was completed and used to determine the absolute configuration of the new albubactins.

MeSH terms

  • Animals
  • Glycolipids* / chemical synthesis
  • Glycolipids* / chemistry
  • Lipopeptides* / biosynthesis
  • Lipopeptides* / chemistry
  • Marine Biology
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Streptomyces* / chemistry
  • Tandem Mass Spectrometry
  • Urochordata / chemistry

Substances

  • Glycolipids
  • Lipopeptides
  • rhamnolipid