Carnosic acid biosynthesis elucidated by a synthetic biology platform

Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3681-6. doi: 10.1073/pnas.1523787113. Epub 2016 Mar 14.


Synthetic biology approaches achieving the reconstruction of specific plant natural product biosynthetic pathways in dedicated microbial "chassis" have provided access to important industrial compounds (e.g., artemisinin, resveratrol, vanillin). However, the potential of such production systems to facilitate elucidation of plant biosynthetic pathways has been underexplored. Here we report on the application of a modular terpene production platform in the characterization of the biosynthetic pathway leading to the potent antioxidant carnosic acid and related diterpenes in Salvia pomifera and Rosmarinus officinalis.Four cytochrome P450 enzymes are identified (CYP76AH24, CYP71BE52, CYP76AK6, and CYP76AK8), the combined activities of which account for all of the oxidation events leading to the biosynthesis of the major diterpenes produced in these plants. This approach develops yeast as an efficient tool to harness the biotechnological potential of the numerous sequencing datasets that are increasingly becoming available through transcriptomic or genomic studies.

Keywords: cytochrome P450; metabolic engineering; terpene; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abietanes / biosynthesis*
  • Abietanes / chemistry
  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Biosynthetic Pathways
  • Biotechnology
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Metabolic Engineering
  • Plant Proteins / genetics
  • Plant Proteins / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Rosmarinus / genetics
  • Rosmarinus / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Salvia / genetics
  • Salvia / metabolism
  • Synthetic Biology / methods


  • Abietanes
  • Antioxidants
  • Plant Proteins
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System
  • salvin