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Endogenous Enzymes Enable Antimicrobial Activity
Name
nihms-1711402.pdf
Description
Accepted version
Size
1.05 MB
Format
Adobe PDF
Checksum (MD5)
ccf9b4a78b8e7c00d557a95ba18a5928
Author(s)
Hetrick, Kenton J
Aguilar Ramos, Miguel A
Raines, Ronald T
Date Issued
2021
Journal
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Citation
Hetrick, Kenton J, Aguilar Ramos, Miguel A and Raines, Ronald T. 2021. "Endogenous Enzymes Enable Antimicrobial Activity." ACS Chemical Biology, 16 (5).
Version
Author's final manuscript
Abstract
In light of the continued threat of antimicrobial-resistant bacteria, new strategies to expand the repertoire of antimicrobial compounds are necessary. Prodrugs are an underexploited strategy in this effort. Here, we report on the enhanced antimicrobial activity of a prodrug toward bacteria having an enzyme capable of its activation. A screen led us to the sulfurol ester of the antibiotic trans-3-(4-chlorobenzoyl)acrylic acid. An endogenous esterase makes Mycolycibacterium smegmatis sensitive to this prodrug. Candidate esterases were identified, and their heterologous production made Escherichia coli sensitive to the ester prodrug. Taken together, these data suggest a new approach to the development of antimicrobial compounds that takes advantage of endogenous enzymatic activities to target specific bacteria.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1021/ACSCHEMBIO.0C00894
