Language
English
Publication Date
6-25-2025
Journal
Journal of the American Chemical Society
DOI
10.1021/jacs.4c17876
PMID
40493376
PMCID
PMC12203648
PubMedCentral® Posted Date
6-27-2025
PubMedCentral® Full Text Version
Author MSS
Abstract
Antibiotics are essential for modern medicine, but their use drives the evolution of antimicrobial resistance (AMR) that limits the long-term efficacy of any one drug. To keep pace with AMR and preserve our ability to treat bacterial infections, it is essential that we identify antibiotics with new structures and targets that are not affected by clinical resistance. Historically, most developmental candidates for antibiotics have come from microbial natural products, as they feature chemical structures and biological activities that have been honed over millions of years of evolution. Unfortunately, as classical bioactivity screens for natural product discovery are blind to the pharmacological properties of their hits, they often identify molecules with functional groups that limit their utility as drugs. One prominent example is actinonin, an inhibitor of bacterial peptide deformylase (PDF) whose activity is dependent on a hydroxamate moiety associated with toxicity
Keywords
Amidohydrolases, Biological Products, Anti-Bacterial Agents, Enzyme Inhibitors, Genome, Bacterial, Hydroxamic Acids, Microbial natural products, genome-mining, biosynthesis
Published Open-Access
yes
Recommended Citation
Jonas H Costa-Martini, Eva E Adams, and Chad W Johnston, "Chemotype- and Target-Driven Genome Mining for a New Natural Product Inhibitor of Bacterial Peptide Deformylase" (2025). Faculty, Staff and Students Publications. 6535.
https://digitalcommons.library.tmc.edu/baylor_docs/6535
Graphical Abstract