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

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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. Pe, 2021. "Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-20959-1
    DOI: 10.1038/s41467-021-20959-1
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    Cited by:

    1. Yifeng Zhang & Jie Gao & Lin Ma & Lichan Tu & Tianyuan Hu & Xiaoyi Wu & Ping Su & Yujun Zhao & Yuan Liu & Dan Li & Jiawei Zhou & Yan Yin & Yuru Tong & Huan Zhao & Yun Lu & Jiadian Wang & Wei Gao & Luq, 2023. "Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Nikolaj Lervad Hansen & Louise Kjaerulff & Quinn Kalby Heck & Victor Forman & Dan Staerk & Birger Lindberg Møller & Johan Andersen-Ranberg, 2022. "Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. 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 Din, 2023. "Functional divergence of CYP76AKs shapes the chemodiversity of abietane-type diterpenoids in genus Salvia," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Abigail E. Bryson & Emily R. Lanier & Kin H. Lau & John P. Hamilton & Brieanne Vaillancourt & Davis Mathieu & Alan E. Yocca & Garret P. Miller & Patrick P. Edger & C. Robin Buell & Björn Hamberger, 2023. "Uncovering a miltiradiene biosynthetic gene cluster in the Lamiaceae reveals a dynamic evolutionary trajectory," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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