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

doi:10.1016/j.bmcl.2020.127651

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 journal › Article › peer-review

3 Citations (Scopus)

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 language	English
Article number	127651
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	30
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2020.127651
Publication status	Published - 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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title = "The food-grade antimicrobial xanthorrhizol targets the enoyl-ACP reductase (FabI) in Escherichia coli",

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.",

author = "Yogiara and Mordukhova, {Elena A.} and Dooil Kim and Kim, {Won Gon} and Hwang, {Jae Kwan} and Pan, {Jae Gu}",

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: {\textcopyright} 2020",

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doi = "10.1016/j.bmcl.2020.127651",

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T1 - The food-grade antimicrobial xanthorrhizol targets the enoyl-ACP reductase (FabI) in Escherichia coli

AU - Yogiara,

AU - Mordukhova, Elena A.

AU - Kim, Dooil

AU - Kim, Won Gon

AU - Hwang, Jae Kwan

AU - Pan, Jae Gu

N1 - 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

PY - 2020/12/15

Y1 - 2020/12/15

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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