Genome-Guided Discovery of the Myxobacterial Thiolactone- Containing Sorangibactins

In this study, an unprecedented myxobacterial siderophore termed sorangibactin was discovered by heterologous expression of a coelibactin-like nonribosomal peptide synthetase (NRPS) gene cluster from the Sorangiineae strain MSr11367 in the host Myxococcus xanthus DK1622. De novo structure elucidation uncovered a linear polycyclic structure consisting of an N-terminal phenol group, an oxazole, tandem N-methyl-thiazolidines, and an unusual C-terminal gamma-thiolactone moiety. Except for the unprecedented oxazoline dehydrogenation to form an oxazole, which we show to be catalyzed by a cytochrome P450-dependent enzyme, other tailoring steps were found necessary for efficient downstream processing. The unusual thioesterase (TE) domain is proposed to select homocysteine or methionine for offloading involving an intramolecular gamma-thiolactone formation. Its active site comprises a rare cysteine, which was found essential for product formation by point mutation to alanine or serine, which both abolished its activity. This unusual release mechanism and the resulting rare thiolactone structure can serve as a starting point for detailed biochemical investigations.

Automated summary

An unprecedented myxobacterial siderophore called sorangibactin was discovered in this study by heterologous expression of a coelibactin-like nonribosomal peptide synthetase (NRPS) gene cluster in a host strain. The structure of sorangibactin was found to be a linear polycyclic structure with multiple rings and functional groups. The study also revealed an unusual release mechanism involving a thioesterase (TE) domain, which can be further investigated for biochemically detailed studies.