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

• Published in: Nature communications Vol. 11; no. 1; pp. 971 - 12
• Main Authors: Tu, Lichan, Su, Ping, Zhang, Zhongren, Gao, Linhui, Wang, Jiadian, Hu, Tianyuan, Zhou, Jiawei, Zhang, Yifeng, Zhao, Yujun, Liu, Yuan, Song, Yadi, Tong, Yuru, Lu, Yun, Yang, Jian, Xu, Cao, Jia, Meirong, Peters, Reuben J., Huang, Luqi, Gao, Wei
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-02-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 101/58; 140/131; 38/22; 38/23; 38/39; 38/77; 38/89; 38/90; 38/91; 631/208/726; 631/449/2667; 631/61/318; 82/80; Abietanes - metabolism; Acids; Anticancer properties; Antineoplastic Agents, Phytogenic - biosynthesis; Antitumor activity; Biosynthesis; Biosynthetic Pathways - genetics; Cytochrome; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochromes P450; Dehydroabietic acid; Diterpenes - metabolism; Drugs, Chinese Herbal - metabolism; Epoxy Compounds - metabolism; Gene Expression Profiling; Genes; Genome, Plant; Genomes; Humanities and Social Sciences; Humans; Metabolic Engineering; Metabolites; Metabolome; Metabolomics; multidisciplinary; Natural products; Oxidation; Oxidation-Reduction; Pancreatic cancer; Phenanthrenes - metabolism; Phylogeny; Plant Proteins - genetics; Plant Proteins - metabolism; Plants, Medicinal - genetics; Plants, Medicinal - metabolism; Science; Science (multidisciplinary); Tripterygium - genetics; Tripterygium - metabolism; Tripterygium wilfordii; Triptolide
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14776-1

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.
Tripterygium wilfordii
is a medical plant that can produce antitumor activity compound triptolide. Here, the authors assemble its genome and identify a cytochrome P450 that can catalyze oxidation of a methyl to the acid moiety of dehydroabietic acid in triptolide biosynthesis by integrating multi-omics data.