title: Metabolic engineering of Saccharomyces cerevisiae for production of fatty acid-derived biofuels and chemicals.
abstract: 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.
authors.affiliation: Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, United States; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States.
authors.forename: Weerawat
authors.initials: W
authors.lastname: Runguphan
authors.affiliation: Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, United States; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, United States; Departments of Chemical and Biomolecular Engineering and Bioengineering, University of California, Berkeley, Berkeley, CA 94720, United States. Electronic address: keasling@berkeley.edu.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics; D056804:Biofuels; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000235:genetics; D005227:Fatty Acids / Q000096:biosynthesis / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D056804:Biofuels; D005227:Fatty Acids; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D064429:Fatty Acid Synthases; C526685:FAS1 protein, S cerevisiae; C577477:FAS2 protein, S cerevisiae
keywords: Biodiesels; Fatty acids; Fatty alcohols; Metabolic engineering; Triacylglycerols; Yeast