Project description: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.
Project description:Natural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism. Continued discovery and sequencing of novel myxobacteria from the environment provides BGCs for the genome mining pipeline. Herein, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America. Nine isolates where determined to be novel species of myxobacteria including representatives from the genera Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium , and Stigmatella . Growth profiles, biochemical assays, and descriptions are provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters. Utilizing complete or near complete genome sequences we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria.