Salinipeptins: Integrated Genomic and Chemical Approaches Reveal Unusual d-Amino Acid-Containing Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) from a Great Salt Lake Streptomyces sp.

Analysis of the full genome of an environmentally unique, halotolerant Streptomyces sp. strain GSL-6C, isolated from the Great Salt Lake, revealed a gene cluster encoding the biosynthesis of the salinipeptins, d-amino-acid-containing members of the rare linaridin subfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs). The sequence organization of the unmodified amino acid residues in salinipeptins A–D (1–4) were suggested by genome annotation, and subsequently, their sequence and post-translational modifications were defined using a range of spectroscopic techniques and chemical derivatization approaches. The salinipeptins are unprecedented linaridins bearing nine d-amino acids, which are uncommon in RiPP natural products and are the first reported in the linaridin subfamily. Whole genome mining of GSL-6C did not reveal any homologues of the reported genes responsible for amino acid epimerization in RiPPs, inferring new epimerases may be involved in the conversion of l- to...