title: Enhancing fatty acid production by the expression of the regulatory transcription factor FadR.
abstract: Fatty acids are important precursors to biofuels. The Escherichia coli FadR is a transcription factor that regulates several processes in fatty acid biosynthesis, degradation, and membrane transport. By tuning the expression of FadR in an engineered E. coli host, we were able to increase fatty acid titer by 7.5-fold over our previously engineered fatty acid-producing strain, reaching 5.2±0.5g/L and 73% of the theoretical yield. The mechanism by which FadR enhanced fatty acid yield was studied by whole-genome transcriptional analysis (microarray) and targeted proteomics. Overexpression of FadR led to transcriptional changes for many genes, including genes involved in fatty acid pathways. The biggest transcriptional changes in fatty acid pathway genes included fabB, fabF, and accA. Overexpression of any of these genes alone did not result in a high yield comparable to fadR expression, indicating that FadR enhanced fatty acid production globally by tuning the expression levels of many genes to optimal levels.
authors.affiliation: Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA.
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Zhang
authors.forename: Mario
authors.initials: M
authors.lastname: Ouellet
authors.forename: Tanveer S
authors.initials: TS
authors.lastname: Batth
authors.forename: Paul D
authors.initials: PD
authors.lastname: Adams
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Petzold
authors.forename: Aindrila
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Jay D
authors.initials: JD
authors.lastname: Keasling
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000103:Acetyl-CoA Carboxylase; D000123:Acetyltransferases; D001426:Bacterial Proteins / Q000502:physiology*; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins; D054889:Fatty Acid Synthase, Type II / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis* / Q000302:isolation & purification; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D024861:Genetic Enhancement / Q000379:methods*; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C057119:FadR protein, Bacteria; D005227:Fatty Acids; D012097:Repressor Proteins; D000123:Acetyltransferases; C557137:fabF protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; C490369:FabB protein, E coli; D054889:Fatty Acid Synthase, Type II; D000103:Acetyl-CoA Carboxylase; C557124:accA protein, E coli