title: Metabolic engineering of Saccharomyces cerevisiae to improve 1-hexadecanol production.
abstract: Fatty alcohols are important components of a vast array of surfactants, lubricants, detergents, pharmaceuticals and cosmetics. We have engineered Saccharomyces cerevisiae to produce 1-hexadecanol by expressing a fatty acyl-CoA reductase (FAR) from barn owl (Tyto alba). In order to improve fatty alcohol production, we have manipulated both the structural genes and the regulatory genes in yeast lipid metabolism. The acetyl-CoA carboxylase gene (ACC1) was over-expressed, which improved 1-hexadecanol production by 56% (from 45mg/L to 71mg/L). Knocking out the negative regulator of the INO1 gene in phospholipid metabolism, RPD3, further enhanced 1-hexadecanol production by 98% (from 71mg/L to 140mg/L). The cytosolic acetyl-CoA supply was next engineered by expressing a heterologous ATP-dependent citrate lyase, which increased the production of 1-hexadecanol by an additional 136% (from 140mg/L to 330mg/L). Through fed-batch fermentation using resting cells, over 1.1g/L 1-hexadecanol can be produced in glucose minimal medium, which represents the highest titer reported in yeast to date.
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Xueyang
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States.
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Lian
authors.affiliation: Department of Chemical and Biomolecular Engineering, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States; Departments of Chemistry, Biochemistry, and Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, United States. Electronic address: zhao5@illinois.edu.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D030161:Avian Proteins / Q000096:biosynthesis / Q000235:genetics; D005233:Fatty Alcohols / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D060847:Metabolic Engineering / Q000379:methods*; D007296:Myo-Inositol-1-Phosphate Synthase / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D020305:Strigiformes / Q000235:genetics / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D005233:Fatty Alcohols; D029701:Saccharomyces cerevisiae Proteins; C005031:cetyl alcohol; D000445:Aldehyde Oxidoreductases; C519641:INO1 protein, S cerevisiae; D007296:Myo-Inositol-1-Phosphate Synthase; D000103:Acetyl-CoA Carboxylase
keywords: Acetyl-CoA; Fatty alcohol; Metabolic engineering; Phospholipid; Regulator; Yeast