Harnessing Yeast Peroxisomes for Biosynthesis of Fatty-Acid-Derived Biofuels and Chemicals with Relieved Side-Pathway Competition

J Am Chem Soc. 2016 Nov 30;138(47):15368-15377. doi: 10.1021/jacs.6b07394. Epub 2016 Oct 31.

Abstract

Establishing efficient synthetic pathways for microbial production of biochemicals is often hampered by competing pathways and/or insufficient precursor supply. Compartmentalization in cellular organelles can isolate synthetic pathways from competing pathways, and provide a compact and suitable environment for biosynthesis. Peroxisomes are cellular organelles where fatty acids are degraded, a process that is inhibited under typical fermentation conditions making them an interesting workhouse for production of fatty-acid-derived molecules. Here, we show that targeting synthetic pathways to peroxisomes can increase the production of fatty-acid-derived fatty alcohols, alkanes and olefins up to 700%. In addition, we demonstrate that biosynthesis of these chemicals in the peroxisomes results in significantly decreased accumulation of byproducts formed by competing enzymes. We further demonstrate that production can be enhanced up to 3-fold by increasing the peroxisome population. The strategies described here could be used for production of other chemicals, especially acyl-CoA-derived molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biofuels*
  • Fatty Acids / chemistry*
  • Fatty Acids / metabolism*
  • Metabolic Networks and Pathways*
  • Molecular Structure
  • Peroxisomes / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / metabolism*

Substances

  • Biofuels
  • Fatty Acids