Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals

Metab Eng. 2014 Jan:21:103-13. doi: 10.1016/j.ymben.2013.07.003. Epub 2013 Jul 27.


As the serious effects of global climate change become apparent and access to fossil fuels becomes more limited, metabolic engineers and synthetic biologists are looking towards greener sources for transportation fuels. In recent years, microbial production of high-energy fuels by economically efficient bioprocesses has emerged as an attractive alternative to the traditional production of transportation fuels. Here, we engineered the budding yeast Saccharomyces cerevisiae to produce fatty acid-derived biofuels and chemicals from simple sugars. Specifically, we overexpressed all three fatty acid biosynthesis genes, namely acetyl-CoA carboxylase (ACC1), fatty acid synthase 1 (FAS1) and fatty acid synthase 2 (FAS2), in S. cerevisiae. When coupled to triacylglycerol (TAG) production, the engineered strain accumulated lipid to more than 17% of its dry cell weight, a four-fold improvement over the control strain. Understanding that TAG cannot be used directly as fuels, we also engineered S. cerevisiae to produce drop-in fuels and chemicals. Altering the terminal "converting enzyme" in the engineered strain led to the production of free fatty acids at a titer of approximately 400 mg/L, fatty alcohols at approximately 100mg/L and fatty acid ethyl esters (biodiesel) at approximately 5 mg/L directly from simple sugars. We envision that our approach will provide a scalable, controllable and economic route to this important class of chemicals.

Keywords: Biodiesels; Fatty acids; Fatty alcohols; Metabolic engineering; Triacylglycerols; Yeast.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyltransferases / biosynthesis
  • Acetyltransferases / genetics
  • Biofuels*
  • Fatty Acid Synthases / biosynthesis
  • Fatty Acid Synthases / genetics
  • Fatty Acids* / biosynthesis
  • Fatty Acids* / genetics
  • Saccharomyces cerevisiae Proteins / biosynthesis
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism


  • Biofuels
  • Fatty Acids
  • Saccharomyces cerevisiae Proteins
  • Acetyltransferases
  • aminoglycoside N1-acetyltransferase
  • Fatty Acid Synthases
  • FAS1 protein, S cerevisiae
  • FAS2 protein, S cerevisiae