Identification and Interrogation of the Herbicidin Biosynthetic Gene Cluster: First Insight into the Biosynthesis of a Rare Undecose Nucleoside Antibiotic

  • J Am Chem Soc. 2017 Nov 22;139(46):16450-16453. doi: 10.1021/jacs.7b08985.
Geng-Min Lin  1 ,  Anthony J Romo  1 ,  Priscilla H Liem  1 ,  Zhang Chen  1 ,  Hung-Wen Liu  1
Affiliations
  • 1. Department of Chemistry, ‡Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, and §Department of Biochemistry, University of Texas at Austin , Austin, Texas 78712, United States.
PMID: 29111702 DOI: 10.1021/jacs.7b08985
Abstract

Herbicidins are adenosine-based nucleoside Antibiotics with an unusual tricyclic undecose core decorated with a (5-hydroxy)tiglyl moiety. Feeding studies are herein reported demonstrating that the tricyclic core is derived from d-glucose and d-ribose, whereas the tiglyl moiety is derived from an intermediate of l-isoleucine catabolism. Identification of the gene cluster for herbicidin A biosynthesis in Streptomyces sp. L-9-10 as well as its verification by heterologous expression in a nonproducing host are described, and the results of in vitro characterization of a carboxyl methyltransferase encoded in the cluster, Her8, are presented. Based on these observations, a biosynthetic pathway is proposed for herbicidins.

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