Discovery of the Biosynthetic Machinery for Stravidins, Biotin Antimetabolites

Rana Montaser, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Stravidins are peptide antibiotics produced by Streptomyces spp. Their antibacterial activity derives from an unusual amiclenomycin monomer, the warhead that inhibits biotin biosynthesis. Despite being discovered over five decades ago, stravidin biosynthesis has remained a mystery. Using our "metabologenomics" platform, we discover new stravidin analogues and identify the novel biosynthetic machinery responsible for their production. Analysis of the newly identified biosynthetic gene cluster (BGC) indicates the unusual amiclenomycin warhead is derived from chorismic acid, with initial steps similar to those involved in p-amino phenylalanine biosynthesis. However, a distinctive decarboxylation retains the nonaromatic character of a key ring and precedes a one-carbon extension to afford the warhead in its bioactive, untriggered state. Strikingly, we also identified two streptavidin genes flanking the new stravidin BGC reported here. This aligns with the known synergistic activity between the biotin-binding activity of streptavidin and the stravidins to antagonize both biotin biogenesis and bacterial growth.

Original languageEnglish (US)
Pages (from-to)1134-1140
Number of pages7
JournalACS chemical biology
Volume15
Issue number5
DOIs
StatePublished - May 15 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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