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

• Published in: Journal of natural products (Washington, D.C.) Vol. 87; no. 7; pp. 1682 - 1693
• Main Authors: Maw, Zacharie A., Grunwald, Alyssa L., Haltli, Bradley A., Cartmell, Christopher, Kerr, Russell G.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 26-07-2024
• Subjects: 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
• ISSN: 0163-3864; 1520-6025; 1520-6025
• DOI: 10.1021/acs.jnatprod.3c01234

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.