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

Nat Commun. 2020 Feb 20;11(1):971. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / metabolism
  • Antineoplastic Agents, Phytogenic / biosynthesis
  • Biosynthetic Pathways / genetics
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Diterpenes / metabolism*
  • Drugs, Chinese Herbal / metabolism
  • Epoxy Compounds / metabolism
  • Gene Expression Profiling
  • Genome, Plant
  • Humans
  • Metabolic Engineering
  • Metabolome
  • Oxidation-Reduction
  • Phenanthrenes / metabolism*
  • Phylogeny
  • Plant Proteins / genetics*
  • Plant Proteins / metabolism*
  • Plants, Medicinal / genetics
  • Plants, Medicinal / metabolism
  • Tripterygium / genetics*
  • Tripterygium / metabolism*


  • Abietanes
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Drugs, Chinese Herbal
  • Epoxy Compounds
  • Phenanthrenes
  • Plant Proteins
  • dehydroabietic acid
  • triptolide
  • Cytochrome P-450 Enzyme System