Scaffold-Adaptive P450 Enzymes Balance Substrate Promiscuity with Catalytic Specificity in Brassicicene Biosynthesis
We investigated the functional plasticity of two P450 enzymes, AbnK and AbnG, in the brassicicene biosynthetic pathway. Through <i>in vivo</i> heterologous expression, feeding assays, and <i>in vitro</i> reactions, we show that these enzymes regio- and stereoselectively transform both 5-8-5 and 5-9-5 terpenoid scaffolds in different ways, supported by computational simulations. AbnK also bridges a missing step in brassicicene A biosynthesis. Our findings demonstrate how controlled promiscuity underpins structural diversity, informing strategies to expand chemoenzymatic synthesis.
Authors
- Zhengxi Hu (ORCID: https://orcid.org/0000-0002-1247-5615)
- Wenling Yuan
- Ying Ye (ORCID: https://orcid.org/0000-0002-7357-7236)
- Juan V. Alegre‐Requena (ORCID: https://orcid.org/0000-0002-0769-7168)
- Yuan Zhou (ORCID: https://orcid.org/0000-0003-2892-0100)
- Fengli Li
- Zhenhua Guan
- Yonghui Zhang (ORCID: https://orcid.org/0000-0002-7222-2142)
- Junjun Liu (ORCID: https://orcid.org/0000-0001-9953-8633)
- Zhe Chen (ORCID: https://orcid.org/0009-0005-2285-2890)
- AWei Che
Institutions
- Universidad de Zaragoza (ES)
- Instituto de Síntesis Química y Catálisis Homogénea (ES)
- Culture Resource (EG)
- Huazhong University of Science and Technology (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-03-31
- DOI
- https://doi.org/10.1021/acs.orglett.5c00656
- Primary Topic
- 14-3-3 protein interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- National Program for Support of Top-notch Young Professionals