TY - JOUR
T1 - Enhancing fatty acid production by the expression of the regulatory transcription factor FadR
AU - Zhang, Fuzhong
AU - Ouellet, Mario
AU - Batth, Tanveer S
AU - Adams, Paul D
AU - Petzold, Christopher J
AU - Mukhopadhyay, Aindrila
AU - Keasling, Jay D
N1 - Copyright © 2012. Published by Elsevier Inc.
PY - 2012/11
Y1 - 2012/11
N2 - 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.
AB - 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.
KW - 3-Oxoacyl-(Acyl-Carrier-Protein) Synthase
KW - Acetyl-CoA Carboxylase
KW - Acetyltransferases
KW - Bacterial Proteins
KW - Escherichia coli
KW - Escherichia coli Proteins
KW - Fatty Acid Synthetase Complex, Type II
KW - Fatty Acids
KW - Gene Expression Regulation, Enzymologic
KW - Genetic Enhancement
KW - Regulatory Elements, Transcriptional
KW - Repressor Proteins
U2 - 10.1016/j.ymben.2012.08.009
DO - 10.1016/j.ymben.2012.08.009
M3 - Journal article
C2 - 23026122
SN - 1096-7176
VL - 14
SP - 653
EP - 660
JO - Metabolic Engineering
JF - Metabolic Engineering
IS - 6
ER -