A Unified Mechanism Reveals the Evolutionary Origin of Enoyl Isomerases
Enoyl isomerases (EIs) and dehydratases (DHs) are critical for diversifying polyketide natural products; however, the underlying mechanism remains controversial. Through a combination of 1H NMR, solvent isotope effect (SIE) analyses, and mutagenesis applied to two bifunctional dehydratase/enoyl isomerases (DH/EIs), a “His-solo” monofunctional EI, and an engineered “Asp-solo” monofunctional EI, we uncovered a unified catalytic mechanism, highlighting the pivotal role of Asp-H2O in tuning the ratio of DH and EI activities. This mechanism not only deciphers the catalytic basis of these enzymes but also provides a comprehensive framework for understanding their evolutionary trajectory from DHs to DH/EIs and ultimately to EIs.
Authors
- Huimin Zhao (ORCID: https://orcid.org/0000-0002-9069-6739)
- Bin Wang (ORCID: https://orcid.org/0000-0003-3688-332X)
- Jinwei Ren (ORCID: https://orcid.org/0000-0001-6835-4962)
- Bing Chen (ORCID: https://orcid.org/0000-0002-1238-3948)
Institutions
- University of Illinois Urbana-Champaign (US)
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- Ecologie microbienne (FR)
- State Key Laboratory of Chemical Engineering (CN)
- Institute of Mechanics (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- ACS Catalysis
- Published
- 2025-08-26
- DOI
- https://doi.org/10.1021/acscatal.5c05457
- Citations
- 2
- Primary Topic
- Protein Structure and Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- National Institutes of Health
- National Key Research and Development Program of China
- Beijing Science and Technology Planning Project