Structure elucidation and biological activities of two classes of peptides produced by the actinomycete, Kitasatospora cystarginea

Abstract

Kitasatospora is a rare genus of Actinobacteria that represents an underexplored resource for the discovery of structurally diverse natural products. To highlight the production of unique metabolites produced by twelve members of this genus, the chemical screening method that combines LC-HRMS with Principal Component Analysis (PCA) was used. This approach identified the production of three novel compounds by K. cystarginea; which were determined to be a lipopeptide and two β-lactone containing peptide analogs, referred to as cystargamide and cystargolides A and B. Their structures were elucidated using NMR and MS/MS, and absolute configurations using advanced Marfey's Method. The therapeutic potential of cystargamide and cystargolides A and B were evaluated in several bioassays. Most notably, cystargolides A and B displayed inhibition of human 20S proteasome with IC50 values of 0.35 and 0.93µM respectively.