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

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, Reuben J. Peters, Luqi Huang () and Wei Gao ()
Additional contact information
Lichan Tu: Capital Medical University
Ping Su: National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences
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

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-14776-1

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