Functional evolution and diversification of CYP82D subfamily members have shaped flavonoid diversification in the genus Scutellaria
Flavonoids, the largest class of polyphenols, exhibit substantial structural and functional diversity, yet their evolutionary diversification and specialized functions remain largely unexplored. The genus Scutellaria is notable for its rich flavonoid diversity, particularly of 6/8-hydroxylated variants biosynthesized by the cytochrome P450 subfamily CYP82D. Our study analyzes metabolic differences between Scutellaria baicalensis and Scutellaria barbata, and the results suggest that CYP82Ds have acquired a broad range of catalytic functions over their evolution. By integrating analyses of metabolic networks and gene evolution across 22 Scutellaria species, we rapidly identified 261 flavonoids and delineated five clades of CYP82Ds associated with various catalytic functions. This approach revealed a unique catalytic mode for 6/8-hydroxylation of flavanone substrates and the first instance of 7-O-demethylation of flavonoid substrates catalyzed by a cytochrome P450. Ancestral sequence reconstruction and functional validation demonstrated that gradual neofunctionalization of CYP82Ds has driven the chemical diversity of flavonoids in the genus Scutellaria throughout its evolutionary history. These findings enhance our understanding of flavonoid diversity, reveal the intricate roles of CYP82Ds in Scutellaria species, and highlight the extensive catalytic versatility of cytochrome P450 members within plant taxa.
Authors
- Junfeng Chen (ORCID: https://orcid.org/0009-0001-7900-5896)
- Tianlin Pei (ORCID: https://orcid.org/0000-0002-3750-5139)
- Chun‐Lei Xiang (ORCID: https://orcid.org/0000-0001-8775-6967)
- Jiadong Hu (ORCID: https://orcid.org/0000-0003-3022-629X)
- Ziding Wu
- W W Chen
- Zhichao Xu (ORCID: https://orcid.org/0000-0002-3935-8865)
- Ranran Gao (ORCID: https://orcid.org/0000-0002-7164-0289)
- Chen Zhang (ORCID: https://orcid.org/0000-0002-6592-9318)
- Qing Li (ORCID: https://orcid.org/0000-0003-3087-4692)
- Qing Zhao (ORCID: https://orcid.org/0000-0001-5468-7600)
- Min He (ORCID: https://orcid.org/0000-0002-3355-0522)
- Shi Qiu (ORCID: https://orcid.org/0000-0003-2336-9161)
- Ying Xiao (ORCID: https://orcid.org/0000-0003-4316-4825)
- Jing Wang
- Rong Wang (ORCID: https://orcid.org/0000-0002-2184-6414)
Institutions
- Kunming Institute of Botany (CN)
- Chinese Academy of Sciences (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- State Administration of Traditional Chinese Medicine of the People's Republic of China (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- Shanghai Institute of Materia Medica (CN)
- Shanghai Chenshan Plant Science Research Center (CN)
- China Academy of Chinese Medical Sciences (CN)
- Northeast Forestry University (CN)
Publication Details
- Journal
- Plant Communications
- Published
- 2024-09-14
- DOI
- https://doi.org/10.1016/j.xplc.2024.101134
- Citations
- 16
- Primary Topic
- Flavonoids in Medical Research
- Type
- article
- Field-Weighted Citation Impact
- 7.17
Funders
- Natural Science Foundation of Shanghai
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Science and Technology Commission of Shanghai Municipality
- Shanghai University of Traditional Chinese Medicine
- Shanghai Key Laboratory of Plant Functional Genomics and Resources
- Health Science Center, University of Tennessee
- National Key Research and Development Program of China