Multienzyme Cascade Catalyzed Skeleton Rearrangement in a Caged Polyketide Biosynthesis
Rearrangement of the skeleton is crucial for improving the structural complexity and diversity of type II polyketide natural products. In this study, we investigated the rearrangement process from a planar aromatic tetracyclic intermediate to the caged lactones, which is managed by five oxidoreductases. We chemically synthesized the proposed linear tetracyclic substrate, validated the transformation process through <i>in vivo</i> and <i>in vitro</i> experiments, and elucidated the enzyme-catalyzed mechanism using isotope labeling. Significantly, a short-chain dehydrogenase TjhD5 was discovered to play a multifunctional role for multistep reactions.
Authors
- Jun Zhou (ORCID: https://orcid.org/0009-0007-8541-3320)
- Gong‐Li Tang (ORCID: https://orcid.org/0000-0003-3149-4683)
- Kuan Zheng (ORCID: https://orcid.org/0000-0001-7549-1877)
- Ran Hong (ORCID: https://orcid.org/0000-0002-7602-539X)
- Xianfeng Hou (ORCID: https://orcid.org/0000-0002-1788-3263)
- Qiuyue Nie (ORCID: https://orcid.org/0000-0002-2805-1462)
Institutions
- Shanghai Institute of Organic Chemistry (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2024-12-31
- DOI
- https://doi.org/10.1021/acs.orglett.4c04412
- Citations
- 2
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.90
Funders
- National Natural Science Foundation of China
- Chinese Academy of Sciences
- Science and Technology Commission of Shanghai Municipality