Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza

Ying Ma, Guanghong Cui (), Tong Chen, Xiaohui Ma, Ruishan Wang, Baolong Jin, Jian Yang, Liping Kang, Jinfu Tang, Changjiangsheng Lai, Yanan Wang, Yujun Zhao, Ye Shen, Wen Zeng, Reuben J. Peters, Xiaoquan Qi (), Juan Guo () and Luqi Huang ()
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Ying Ma: China Academy of Chinese Medical Sciences
Guanghong Cui: China Academy of Chinese Medical Sciences
Tong Chen: China Academy of Chinese Medical Sciences
Xiaohui Ma: Yunnan University of Traditional Chinese Medicine
Ruishan Wang: China Academy of Chinese Medical Sciences
Baolong Jin: China Academy of Chinese Medical Sciences
Jian Yang: China Academy of Chinese Medical Sciences
Liping Kang: China Academy of Chinese Medical Sciences
Jinfu Tang: China Academy of Chinese Medical Sciences
Changjiangsheng Lai: China Academy of Chinese Medical Sciences
Yanan Wang: China Academy of Chinese Medical Sciences
Yujun Zhao: China Academy of Chinese Medical Sciences
Ye Shen: China Academy of Chinese Medical Sciences
Wen Zeng: China Academy of Chinese Medical Sciences
Reuben J. Peters: Iowa State University
Xiaoquan Qi: Institute of Botany, the Chinese Academy of Sciences
Juan Guo: China Academy of Chinese Medical Sciences
Luqi Huang: China Academy of Chinese Medical Sciences

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Tanshinones are the bioactive nor-diterpenoid constituents of the Chinese medicinal herb Danshen (Salvia miltiorrhiza). These groups of chemicals have the characteristic furan D-ring, which differentiates them from the phenolic abietane-type diterpenoids frequently found in the Lamiaceae family. However, how the 14,16-epoxy is formed has not been elucidated. Here, we report an improved genome assembly of Danshen using a highly homozygous genotype. We identify a cytochrome P450 (CYP71D) tandem gene array through gene expansion analysis. We show that CYP71D373 and CYP71D375 catalyze hydroxylation at carbon-16 (C16) and 14,16-ether (hetero)cyclization to form the D-ring, whereas CYP71D411 catalyzes upstream hydroxylation at C20. In addition, we discover a large biosynthetic gene cluster associated with tanshinone production. Collinearity analysis indicates a more specific origin of tanshinones in Salvia genus. It illustrates the evolutionary origin of abietane-type diterpenoids and those with a furan D-ring in Lamiaceae.

Date: 2021
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DOI: 10.1038/s41467-021-20959-1

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