The Isolation and Structure Elucidation of Spirotetronate Lobophorins A, B, and H8 from Streptomyces sp. CB09030 and Their Biosynthetic Gene Cluster.

Lobophorins (LOBs) are a growing family of spirotetronate natural products with significant cytotoxicity, anti-inflammatory, and antibacterial activities. Herein, we report the transwell-based discovery of Streptomyces sp. CB09030 from a panel of 16 in-house Streptomyces strains, which has significant anti-mycobacterial activity and produces LOB A ( 1 ), LOB B ( 2 ), and LOB H8 ( 3 ). Genome sequencing and bioinformatic analyses revealed the potential biosynthetic gene cluster (BGC) for 1 - 3 , which is highly homologous with the reported BGCs for LOBs. However, the glycosyltransferase LobG1 in S . sp. CB09030 has certain point mutations compared to the reported LobG1. Finally, LOB analogue 4 (O-β-D-kijanosyl-(1→17)-kijanolide) was obtained through an acid-catalyzed hydrolysis of 2 . Compounds 1 - 4 showed different antibacterial activities against Mycobacterium smegmatis and Bacillus subtilis , which revealed the varying roles of different sugars in their antibacterial activities.