Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia

Jiadong Hu, Shi Qiu (), Feiyan Wang, Qing Li, Chun-Lei Xiang, Peng Di, Ziding Wu, Rui Jiang, Jinxing Li, Zhen Zeng, Jing Wang, Xingxing Wang, Yuchen Zhang, Shiyuan Fang, Yuqi Qiao, Jie Ding, Yun Jiang, Zhichao Xu (), Junfeng Chen () and Wansheng Chen ()
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Jiadong Hu: Shanghai University of Traditional Chinese Medicine
Shi Qiu: Shanghai University of Traditional Chinese Medicine
Feiyan Wang: Shanghai University of Traditional Chinese Medicine
Qing Li: Second Affiliated Hospital of Navy Medical University
Chun-Lei Xiang: Chinese Academy of Sciences
Peng Di: Jilin Agricultural University
Ziding Wu: Shanghai University of Traditional Chinese Medicine
Rui Jiang: Shanghai University of Traditional Chinese Medicine
Jinxing Li: Shanghai University of Traditional Chinese Medicine
Zhen Zeng: Shanghai University of Traditional Chinese Medicine
Jing Wang: Shanghai University of Traditional Chinese Medicine
Xingxing Wang: Shanghai University of Traditional Chinese Medicine
Yuchen Zhang: Shanghai University of Traditional Chinese Medicine
Shiyuan Fang: Shanghai University of Traditional Chinese Medicine
Yuqi Qiao: Shanghai University of Traditional Chinese Medicine
Jie Ding: Shanghai Chenshan Botanical Garden
Yun Jiang: Shanghai Chenshan Botanical Garden
Zhichao Xu: Northeast Forestry University
Junfeng Chen: Shanghai University of Traditional Chinese Medicine
Wansheng Chen: Shanghai University of Traditional Chinese Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The genus Salvia L. (Lamiaceae) comprises myriad distinct medicinal herbs, with terpenoids as one of their major active chemical groups. Abietane-type diterpenoids (ATDs), such as tanshinones and carnosic acids, are specific to Salvia and exhibit taxonomic chemical diversity among lineages. To elucidate how ATD chemical diversity evolved, we carried out large-scale metabolic and phylogenetic analyses of 71 Salvia species, combined with enzyme function, ancestral sequence and chemical trait reconstruction, and comparative genomics experiments. This integrated approach showed that the lineage-wide ATD diversities in Salvia were induced by differences in the oxidation of the terpenoid skeleton at C-20, which was caused by the functional divergence of the cytochrome P450 subfamily CYP76AK. These findings present a unique pattern of chemical diversity in plants that was shaped by the loss of enzyme activity and associated catalytic pathways.

Date: 2023
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DOI: 10.1038/s41467-023-40401-y

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