Butuanimides, Fatty Acid Synthesis-Inhibiting Antibiotics from Symbiotic Bacteria
identified the ACC carboxyl transferase (CT) subunit as responsible for butuanimide antibacterial activity. The andrimid-like peptide-imide moiety is attached to a longer, halogenated polyene chain that initiates with an unusual starter unit likely derived from phenylalanine. The resulting epoxyquinone is unstable in solution over a period of hours to days, enabling redox control of antibiotic action. Comparison of the hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) biosynthetic gene clusters of butuanimides and andrimid suggests the repurposing of a key phenylalanine-derived motif. The butuanimide structures link the thailandamide- and andrimid-class ACC inhibitors, which should aid ongoing efforts in the development of ACC inhibitors to treat multidrug-resistant infections.
Authors
- Margo G. Haygood (ORCID: https://orcid.org/0000-0001-5277-9544)
- Colin Manoil (ORCID: https://orcid.org/0000-0001-6773-3434)
- Marvin A. Altamia (ORCID: https://orcid.org/0000-0002-8625-767X)
- Eric W. Schmidt (ORCID: https://orcid.org/0000-0001-5839-694X)
- Mark Jeremiah B. Cleofas
- Hiroaki Naka (ORCID: https://orcid.org/0000-0002-6208-2270)
- Bailey W. Miller (ORCID: https://orcid.org/0000-0003-3204-3235)
- Albebson L. Lim (ORCID: https://orcid.org/0000-0001-9972-3425)
- Jared T. Seale (ORCID: https://orcid.org/0000-0003-3505-4861)
- Gisela P. Concepción (ORCID: https://orcid.org/0000-0002-2216-5637)
- Jose Miguel D. Robes (ORCID: https://orcid.org/0000-0002-5593-712X)
- Jeannie Bailey (ORCID: https://orcid.org/0000-0003-1436-3729)
- Noel Lacerna
Institutions
- University of Washington (US)
- University of Utah (US)
- University of the Philippines Diliman (PH)
Publication Details
- Journal
- ACS Chemical Biology
- Published
- 2026-04-28
- DOI
- https://doi.org/10.1021/acschembio.6c00130
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institute of Allergy and Infectious Diseases
- Fogarty International Center