The food-grade antimicrobial xanthorrhizol targets the enoyl-ACP reductase (FabI) in Escherichia coli

Bioorg Med Chem Lett. 2020 Dec 15;30(24):127651. doi: 10.1016/j.bmcl.2020.127651. Epub 2020 Oct 29.

Abstract

Xanthorrhizol, isolated from the Indonesian Java turmeric Curcuma xanthorrhiza, displays broad-spectrum antibacterial activity. We report herein the evidence that mechanism of action of xanthorrhizol may involve FabI, an enoyl-(ACP) reductase, inhibition. The predicted Y156V substitution in the FabI enzyme promoted xanthorrhizol resistance, while the G93V mutation originally known for triclosan resistance was not effective against xanthorrhizol. Two other mutations, F203L and F203V, conferred FabI enzyme resistance to both xanthorrhizol and triclosan. These results showed that xanthorrhizol is a food-grade antimicrobial compound targeting FabI but with a different mode of binding from triclosan.

Keywords: Enoyl-ACP reductase; FabI; Food-grade antimicrobial; Mechanism of action; Xanthorrhizol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology*
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / microbiology
  • Escherichia coli Proteins / antagonists & inhibitors*
  • Escherichia coli Proteins / metabolism
  • Fatty Acid Synthase, Type II / antagonists & inhibitors
  • Fatty Acid Synthase, Type II / metabolism
  • Food Additives / pharmacology*
  • Humans
  • Molecular Docking Simulation
  • Phenols / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Escherichia coli Proteins
  • Food Additives
  • Phenols
  • xanthorrhizol
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • fabI protein, E coli
  • Fatty Acid Synthase, Type II