Molecular cloning and characterization of a cytochrome P450 taxoid 9á-hydroxylase in Ginkgo biloba cells

Biochem Biophys Res Commun. 2014 Jan 17;443(3):938-43. doi: 10.1016/j.bbrc.2013.12.104. Epub 2013 Dec 28.

Abstract

Taxol is a well-known effective anticancer compound. Due to the inability to synthesize sufficient quantities of taxol to satisfy commercial demand, a biotechnological approach for a large-scale cell or cell-free system for its production is highly desirable. Several important genes in taxol biosynthesis are currently still unknown and have been shown to be difficult to isolate directly from Taxus, including the gene encoding taxoid 9α-hydroxylase. Ginkgo biloba suspension cells exhibit taxoid hydroxylation activity and provides an alternate means of identifying genes encoding enzymes with taxoid 9α-hydroxylation activity. Through analysis of high throughput RNA sequencing data from G. biloba, we identified two candidate genes with high similarity to Taxus CYP450s. Using in vitro cell-free protein synthesis assays and LC-MS analysis, we show that one candidate that belongs to the CYP716B, a subfamily whose biochemical functions have not been previously studied, possessed 9α-hydroxylation activity. This work will aid future identification of the taxoid 9α-hydroxylase gene from Taxus sp.

Keywords: CYP450; Cell-free protein synthesis system; Ginkgo biloba; LC–MS; Taxoid 9α-hydroxylase; Taxol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Acetates / metabolism
  • Biocatalysis
  • Chromatography, High Pressure Liquid
  • Cloning, Molecular
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Diterpenes / chemistry
  • Diterpenes / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Ginkgo biloba / cytology*
  • Ginkgo biloba / enzymology*
  • Ginkgo biloba / genetics
  • Mass Spectrometry
  • Molecular Sequence Data
  • Sequence Analysis, Protein

Substances

  • Acetates
  • Diterpenes
  • sinenxan A
  • Cytochrome P-450 Enzyme System

Associated data

  • GENBANK/KF773140
  • GENBANK/KF773141