Peptide surfactants with post-translational C-methylations that promote bacterial development

Abstract

Bacteria produce a variety of peptides to mediate nutrient acquisition, microbial interactions and other physiological processes. Of special interest are surface-active peptides that aid in growth and development. Herein we report the structure and characterization of clavusporins, unusual and hydrophobic ribosomal peptides with multiple C-methylations at unactivated carbon centers, which help drastically reduce the surface tension of water and thereby aid in Streptomyces development. The peptides are synthesized by a previously uncharacterized protein superfamily, termed DUF5825, in conjunction with a vitamin B12-dependent radical S-adenosylmethionine metalloenzyme. The operon encoding clavusporins is widespread among actinomycete bacteria, suggesting a prevalent role for clavusporins as morphogens in erecting aerial hyphae and thereby advancing sporulation and proliferation. Soil-dwelling Actinomyces bacteria have been found to employ an iterative B12-dependent radical S-adenosylmethionine metalloenzyme to synthesize hypermethylated ribosomal peptides. These amphiphilic peptides serve as surface-active agents and promote the growth of aerial, reproductive structures.