Synthesis of 11-carbon terpenoids in yeast using protein and metabolic engineering

Nat Chem Biol. 2018 Dec;14(12):1090-1098. doi: 10.1038/s41589-018-0166-5. Epub 2018 Nov 14.


One application of synthetic biology is the redesign of existing biological systems to acquire new functions. In this context, expanding the chemical code underlying key biosynthetic pathways will lead to the synthesis of compounds with new structures and potentially new biological activities. Terpenoids are a large group of specialized metabolites with numerous applications. Yet, being synthesized from five-carbon units, they are restricted to distinct classes that differ by five carbon atoms (C10, C15, C20, etc.). To expand the diversity of terpenoid structures, we engineered yeast cells to synthesize a noncanonical building block with 11 carbons, and produced 40 C11 terpene scaffolds that can form the basis for an entire terpenoid class. By identifying a single-residue switch that converts C10 plant monoterpene synthases to C11-specific enzymes, we engineered dedicated synthases for C11 terpene production. This approach will enable the systematic expansion of the chemical space accessed by terpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism
  • Cyanobacteria / enzymology
  • Cyanobacteria / genetics
  • Diphosphates / metabolism
  • Diterpenes / metabolism
  • Metabolic Engineering / methods*
  • Protein Engineering / methods
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Synthetic Biology / methods
  • Terpenes / chemical synthesis*
  • Terpenes / metabolism


  • Diphosphates
  • Diterpenes
  • Recombinant Proteins
  • Terpenes
  • geranyl diphosphate
  • Alkyl and Aryl Transferases
  • terpene synthase