Charting an Unexplored Streptococcal Biosynthetic Landscape Reveals a Unique Peptide Cyclization Motif.

TitleCharting an Unexplored Streptococcal Biosynthetic Landscape Reveals a Unique Peptide Cyclization Motif.
Publication TypeJournal Article
Year of Publication2018
AuthorsBushin, LB, Clark, KA, Pelczer, I, Seyedsayamdost, MR
JournalJ Am Chem Soc
Volume140
Issue50
Pagination17674-17684
Date Published2018 12 19
ISSN1520-5126
KeywordsAmino Acid Sequence, Bacterial Proteins, Computational Biology, Cyclization, Escherichia coli, Indoles, Multigene Family, Oxidoreductases, Peptides, Cyclic, Protein Processing, Post-Translational, Quorum Sensing, S-Adenosylmethionine, Streptococcus
Abstract

Peptide natural products are often used as signals or antibiotics and contain unusual structural modifications, thus providing opportunities for expanding our understanding of Nature's therapeutic and biosynthetic repertoires. Herein, we have investigated the under-explored biosynthetic potential of Streptococci, prevalent bacteria in mammalian microbiomes that include mutualistic, commensal, and pathogenic members. Using a new bioinformatic search strategy, in which we linked the versatile radical S-adenosylmethionine (RaS) enzyme superfamily to an emerging class of natural products in the context of quorum sensing control, we identified numerous, uncharted biosynthetic loci. Focusing on one such locus, we identified an unprecedented post-translational modification, consisting of a tetrahydro[5,6]benzindole cyclization motif in which four unactivated positions are linked by two C-C bonds in a regio- and stereospecific manner by a single RaS enzyme. Our results expand the scope of reactions that microbes have at their disposal in concocting complex ribosomal peptides.

DOI10.1021/jacs.8b10266
Alternate JournalJ. Am. Chem. Soc.
PubMed ID30398325