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

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.