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

Leah B. Bushin, Kenzie A. Clark, István Pelczer, Mohammad R. Seyedsayamdost

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)17674-17684
Number of pages11
JournalJournal of the American Chemical Society
Issue number50
StatePublished - Dec 19 2018

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


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