Enhanced (S)-linalool production by fusion expression of farnesyl diphosphate synthase and linalool synthase in Saccharomyces cerevisiae

J Appl Microbiol. 2016 Jul;121(1):187-95. doi: 10.1111/jam.13105. Epub 2016 May 27.

Abstract

Aims: In order to improve the availability of geranyl diphosphate (GPP) in the mevalonate pathway for enhancing (S)-linalool production in Saccharomyces cerevisiae.

Methods and results: A (S)-linalool synthase (LIS): AaLS1 from Actinidia arguta was coexpressed with FPPS with different peptide linkers to redirect the flux from geranyl diphosphate (GPP) to (S)-linalool production in S. cerevisiae. The strain with the best peptide linker ((GGGGS)3 ), produced 101·55 ± 2·97 μg l(-1) (S)-linalool, a 69·7% increase compared to those with two independent LIS and FPPS expressed. In a 3-l fermenter, the (S)-linalool titre was further improved to 240·64 ± 5·31 μg l(-1) .

Conclusions: The results demonstrate that the fusion proteins catalysing consecutive steps in a metabolic pathway significantly improved the (S)-linalool production with GPP as precursor.

Significance and impact of the study: The fusion protein strategy co-expressing AaLS1 and FPPS, assembled with a long peptide linker made S. cerevisiae produced the highest reported (S)-Linalool titre to date.

Keywords: biotechnology; enzymes; fermentation biotechnology; gene expression.

MeSH terms

  • Actinidia / enzymology*
  • Acyclic Monoterpenes
  • Diphosphates / metabolism
  • Diterpenes / metabolism
  • Gene Expression
  • Geranyltranstransferase / genetics
  • Geranyltranstransferase / metabolism*
  • Hydro-Lyases / genetics
  • Hydro-Lyases / metabolism*
  • Metabolic Networks and Pathways
  • Monoterpenes / chemistry
  • Monoterpenes / metabolism*
  • Plant Proteins / genetics*
  • Plant Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Acyclic Monoterpenes
  • Diphosphates
  • Diterpenes
  • Monoterpenes
  • Plant Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • geranyl diphosphate
  • linalool
  • Geranyltranstransferase
  • Hydro-Lyases
  • S-linalool synthase