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Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis

Author

Listed:
  • Lichan Tu

    (Capital Medical University
    Capital Medical University)

  • Ping Su

    (National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences
    The Scripps Research Institute)

  • Zhongren Zhang

    (Novogene Bioinformatics Institute)

  • Linhui Gao

    (Capital Medical University)

  • Jiadian Wang

    (Capital Medical University)

  • Tianyuan Hu

    (Capital Medical University)

  • Jiawei Zhou

    (Capital Medical University)

  • Yifeng Zhang

    (Capital Medical University)

  • Yujun Zhao

    (National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences)

  • Yuan Liu

    (Capital Medical University)

  • Yadi Song

    (Capital Medical University)

  • Yuru Tong

    (National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences)

  • Yun Lu

    (Capital Medical University)

  • Jian Yang

    (National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences)

  • Cao Xu

    (University of Chinese Academy of Sciences)

  • Meirong Jia

    (Iowa State University)

  • Reuben J. Peters

    (Iowa State University)

  • Luqi Huang

    (National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences)

  • Wei Gao

    (Capital Medical University
    Capital Medical University
    Capital Medical University)

Abstract

Triptolide is a trace natural product of Tripterygium wilfordii. It has antitumor activities, particularly against pancreatic cancer cells. Identification of genes and elucidation of the biosynthetic pathway leading to triptolide are the prerequisite for heterologous bioproduction. Here, we report a reference-grade genome of T. wilfordii with a contig N50 of 4.36 Mb. We show that copy numbers of triptolide biosynthetic pathway genes are impacted by a recent whole-genome triplication event. We further integrate genomic, transcriptomic, and metabolomic data to map a gene-to-metabolite network. This leads to the identification of a cytochrome P450 (CYP728B70) that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis. We think the genomic resource and the candidate genes reported here set the foundation to fully reveal triptolide biosynthetic pathway and consequently the heterologous bioproduction.

Suggested Citation

  • Lichan Tu & Ping Su & Zhongren Zhang & Linhui Gao & Jiadian Wang & Tianyuan Hu & Jiawei Zhou & Yifeng Zhang & Yujun Zhao & Yuan Liu & Yadi Song & Yuru Tong & Yun Lu & Jian Yang & Cao Xu & Meirong Jia , 2020. "Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14776-1
    DOI: 10.1038/s41467-020-14776-1
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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. Wei Sun & Qinggang Yin & Huihua Wan & Ranran Gao & Chao Xiong & Chong Xie & Xiangxiao Meng & Yaolei Mi & Xiaotong Wang & Caixia Wang & Weiqiang Chen & Ziyan Xie & Zheyong Xue & Hui Yao & Peng Sun & Xu, 2023. "Characterization of the horse chestnut genome reveals the evolution of aescin and aesculin biosynthesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Xiao Feng & Qipian Chen & Weihong Wu & Jiexin Wang & Guohong Li & Shaohua Xu & Shao Shao & Min Liu & Cairong Zhong & Chung-I Wu & Suhua Shi & Ziwen He, 2024. "Genomic evidence for rediploidization and adaptive evolution following the whole-genome triplication," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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