Bacterially derived non-ribosomally synthesized peptides : isolation, structural elucidation, total synthesis and biological investigation

Abstract

Siderophores are non-ribosomally derived peptides, and are key components in bacterial virulence and in the bacterial endogenous secondary metabolome. Therefore, they provide a unique insight into bacterial infection and potential treatments. As such, we have isolated two bacterial siderophores, the first being produced by a novel Actinomadura species. We carried out a de novo structural determination, utilising NMR, HMRS and Marfey’s analysis, allowing us to identify the isolated siderophore as madurastatin C1. This work also allowed us to determine the absolute stereochemistry of madurastatin C1 and ultimately reassigned the structures of the madurastatin family of siderophores. This culminated in a publication in the ACS Journal of Natural Products in early 2017. As a continuation of this work, the total synthesis of madurastatin C1 has been completed. A second novel bacterial strain yielded a novel siderophore like peptide, with structural similarities to the known siderophores; chlorocatechelins. Once again the structure was elucidated via NMR and HRMS with the stereochemistry assigned through Marfey’s analysis. The total synthesis of this novel siderophore was completed, and the synthetic material used in biological studies, confirming the efficacy of the originally isolated natural product.