Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production

J Biol Chem. 2012 Apr 6;287(15):12121-31. doi: 10.1074/jbc.M111.317669. Epub 2012 Feb 15.

Abstract

The labdanoid diterpene alcohol cis-abienol is a major component of the aromatic oleoresin of balsam fir (Abies balsamea) and serves as a valuable bioproduct material for the fragrance industry. Using high-throughput 454 transcriptome sequencing and metabolite profiling of balsam fir bark tissue, we identified candidate diterpene synthase sequences for full-length cDNA cloning and functional characterization. We discovered a bifunctional class I/II cis-abienol synthase (AbCAS), along with the paralogous levopimaradiene/abietadiene synthase and isopimaradiene synthase, all of which are members of the gymnosperm-specific TPS-d subfamily. The AbCAS-catalyzed formation of cis-abienol proceeds via cyclization and hydroxylation at carbon C-8 of a postulated carbocation intermediate in the class II active site, followed by cleavage of the diphosphate group and termination of the reaction sequence without further cyclization in the class I active site. This reaction mechanism is distinct from that of synthases of the isopimaradiene- or levopimaradiene/abietadiene synthase type, which employ deprotonation reactions in the class II active site and secondary cyclizations in the class I active site, leading to tricyclic diterpenes. Comparative homology modeling suggested the active site residues Asp-348, Leu-617, Phe-696, and Gly-723 as potentially important for the specificity of AbCAS. As a class I/II bifunctional enzyme, AbCAS is a promising target for metabolic engineering of cis-abienol production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abies / chemistry
  • Abies / enzymology*
  • Abies / genetics
  • Amino Acid Substitution
  • Biocatalysis
  • Catalytic Domain
  • Diterpenes / chemistry*
  • Diterpenes / metabolism
  • High-Throughput Nucleotide Sequencing
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Naphthols / chemistry*
  • Naphthols / metabolism
  • Perfume*
  • Phylogeny
  • Plant Bark / chemistry
  • Plant Proteins / chemistry
  • Plant Proteins / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Transcriptome*

Substances

  • Diterpenes
  • Naphthols
  • Perfume
  • Plant Proteins
  • abienol

Associated data

  • GENBANK/JN254805
  • GENBANK/JN254806
  • GENBANK/JN254807
  • GENBANK/JN254808