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

Yogiara, Elena A. Mordukhova, Dooil Kim, Won Gon Kim, Jae Kwan Hwang, Jae Gu Pan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number127651
JournalBioorganic and Medicinal Chemistry Letters
Volume30
Issue number24
DOIs
Publication statusPublished - 2020 Dec 15

Bibliographical note

Funding Information:
We thank from Dr. Thomas J Silhavy (Princeton, New Jersey, USA) for E. coli NR693. This work was supported by the National Research Foundation of Korea (NRF) Grants (NRF-2017 R1A2B3005239).

Publisher Copyright:
© 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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