Antimicrobial resistance is an urgent global public health problem that has made the search for new antibiotics essential. Ribosomally synthesized and post-translationally modified peptides are a promising new class of antibiotics and in this work, we report site-selective modification of their dehydroamino acids by β-amination in order to increase water solubility: the singly modified thiopeptide Thiostrepton showed an increase up to 35-fold and minimum inhibitory concentration tests demonstrated that the antimicrobial activity was still good, albeit lower than the natural peptide.

Abstract

We report the efficient and site selective modification of non-canonical dehydroamino acids in ribosomally synthesized and post-transationally modified peptides (RiPPs) by β-amination. The singly modified thiopeptide Thiostrepton showed an up to 35-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity remained good, albeit lower than the unmodified peptide. Also the lanthipeptide nisin could be modified using this method.