title: Production of medium chain length fatty alcohols from glucose in Escherichia coli.
abstract: Metabolic engineering offers the opportunity to produce a wide range of commodity chemicals that are currently derived from petroleum or other non-renewable resources. Microbial synthesis of fatty alcohols is an attractive process because it can control the distribution of chain lengths and utilize low cost fermentation substrates. Specifically, primary alcohols with chain lengths of 12 to 14 carbons have many uses in the production of detergents, surfactants, and personal care products. The current challenge is to produce these compounds at titers and yields that would make them economically competitive. Here, we demonstrate a metabolic engineering strategy for producing fatty alcohols from glucose. To produce a high level of 1-dodecanol and 1-tetradecanol, an acyl-ACP thioesterase (BTE), an acyl-CoA ligase (FadD), and an acyl-CoA/aldehyde reductase (MAACR) were overexpressed in an engineered strain of Escherichia coli. Yields were improved by balancing expression levels of each gene, using a fed-batch cultivation strategy, and adding a solvent to the culture for extracting the product from cells. Using these strategies, a titer of over 1.6 g/L fatty alcohol with a yield of over 0.13 g fatty alcohol/g carbon source was achieved. These are the highest reported yield of fatty alcohols produced from glucose in E. coli.
authors.affiliation: Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 3629 Engineering Hall, 1415 Engineering Drive, Madison, WI 53706, United States; Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53706, United States.
authors.forename: J Tyler
authors.initials: JT
authors.lastname: Youngquist
authors.forename: Martin H
authors.initials: MH
authors.lastname: Schumacher
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Rose
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Raines
authors.forename: Mark C
authors.initials: MC
authors.lastname: Politz
authors.forename: Matthew F
authors.initials: MF
authors.lastname: Copeland
authors.forename: Brian F
authors.initials: BF
authors.lastname: Pfleger
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D007851:Dodecanol / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005233:Fatty Alcohols / Q000378:metabolism*; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D060847:Metabolic Engineering; D016958:Pseudomonas putida / Q000201:enzymology / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D005233:Fatty Alcohols; D011994:Recombinant Proteins; D007851:Dodecanol; D005947:Glucose; C020940:myristyl alcohol
keywords: ACL; ACR; Acyl-CoA reductase; BTE; Cx; Dodecanol; Escherichia coli; Fatty alcohol; GC/MS; MAACR; Marinobacter aquaeolei VT8 ACR; PCR; Tetradecanol; Thioesterase; Umbellularia californica thioesterase; acyl CoA ligase; acyl CoA reductase; fatty acid or alcohol species containing × number of carbon atoms; gas chromatography mass spectrometry; polymerase chain reaction