Deciphering the Biosynthesis of TDP-β-l-oleandrose in Avermectin

J Nat Prod. 2020 Oct 23;83(10):3199-3206. doi: 10.1021/acs.jnatprod.0c00902. Epub 2020 Sep 24.

Abstract

Avermectin (AVM) refers to eight macrolides containing a common l-oleandrosyl disaccharide chain indispensable to their antiparasitic bioactivities. We delineated the biosynthetic pathway of TDP-β-l-oleandrose (1), the sugar donor of AVM, by characterizing AveBVIII, AveBV, and AveBVII as TDP-sugar 3-ketoreductase, 5-epimerase, and 3-O-methyltransferase, respectively. On the basis of this pathway, we successfully reconstituted the biosynthesis of 1 in Escherichia coli. Our work completes the biosynthetic pathway of AVM and lays a solid foundation for further studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents
  • Computational Biology
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Deoxy Sugars / biosynthesis*
  • Escherichia coli / enzymology
  • Escherichia coli / metabolism
  • Hexoses / biosynthesis*
  • Ivermectin / analogs & derivatives*
  • Ivermectin / chemical synthesis
  • Methyltransferases / metabolism
  • Molecular Structure
  • UDPglucose 4-Epimerase / metabolism

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Deoxy Sugars
  • Hexoses
  • oleandrose
  • Ivermectin
  • avermectin
  • Methyltransferases
  • UDPglucose 4-Epimerase