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

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 400mg/L, fatty alcohols at approximately 100mg/L and fatty acid ethyl esters (biodiesel) at approximately 5mg/L directly from simple sugars. We envision that our approach will provide a scalable, controllable and economic route to this important class of chemicals. •We engineer Saccharomyces cerevisiae to make fatty acid-derived biofuels from sugars.•The engineered strain accumulates lipid to more than 17% of its dry cell weight.•The best fatty acid-producing strain produces about 400mg/L free fatty acids.•The best fatty alcohol-producing strain produces about 100mg/L fatty alcohols.•The best biodiesel-producing strain produces about 5mg/L biodiesel.