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

TitleSalinipeptins: 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
Publication TypeJournal Article
Year of Publication2019
AuthorsShang Z., Winter J.M, Kauffman CA, Yang I., Fenical W
JournalAcs Chemical Biology
Volume14
Pagination415-425
Date Published2019/03
Type of ArticleArticle
ISBN Number1554-8929
Accession NumberWOS:000461844100014
KeywordsBiochemistry & Molecular Biology; biosynthesis; cell; conversion; cypemycin; d-alanine; insights; member; natural-products; serine
Abstract

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 D-amino acids. In addition, the N-oxide and dimethylimidazolidin-4-one moieties in salinipeptins B and C, which are modified from N,N-dimethylalanine, are unknown in bacterial peptides. The three-dimensional structure of salinipeptin A, possessing four loops generated by significant hydrogen bonding, was established on the basis of observed nuclear Overhauser effect (NOE) correlations. This study demonstrates that integration of genomic information early in chemical analysis significantly facilitates the discovery and structure characterization of novel microbial secondary metabolites.

DOI10.1021/acschembio.8b01058
Short TitleACS Chem. Biol.
Student Publication: 
No
sharknado