Structure Elucidation and Biosynthesis of Nannosterols A and B, Myxobacterial Sterols from Nannocystis sp. MNa10993

Myxobacteria represent an underinvestigated source of chemically diverse and biologically active secondary metabolites. Here, we report the discovery, isolation, structure elucidation, and biological evaluation of two new bacterial sterols, termed nannosterols A and B (1, 2), from the terrestrial myxobacterium Nannocystis sp. (MNa10993). Nannosterols feature a cholestanol core with numerous modifications including a secondary alcohol at position C-15, a terminal vicinal diol side chain at C-24-C-25 (1, 2), and a hydroxy group at the angular methyl group at C-18 (2), which is unprecedented for bacterial sterols. Another rare chemical feature of bacterial triterpenoids is a ketone group at position C-7, which is also displayed by 1 and 2. The combined exploration based on myxobacterial high-resolution secondary metabolome data and genomic in silico investigations exposed the nannosterols as frequently produced sterols within the myxobacterial suborder of Nannocystineae. The discovery of the nannosterols provides insights into the biosynthesis of these new myxobacterial sterols, with implications in understanding the evolution of sterol production by prokaryotes.

Automated summary

The study reports the discovery, isolation, structure elucidation, and biological evaluation of two new bacterial sterols, nannosterols A and B, from the terrestrial myxobacterium Nannocystis sp. These nannosterols features unique modifications and chemical features, such as a secondary alcohol group at position C-15 and a terminal vicinal diol side chain at C-24-C-25, which have not been observed in bacterial sterols before. The investigation based on myxobacterial high-resolution secondary metabolome data and genomic in silico investigations revealed that nannosterols are frequently produced sterols within the myxobacterial suborder of Nannocystineae. The discovery of nannosterols provides insights into the biosynthesis and evolution of sterols by prokaryotes.