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 - Funding Information:
The authors would like to thank Harry Beller and Ee-Been Goh for discussion and critical reading of the manuscript. This work was supported in part by the Synthetic Biology Engineering Research Center , which is funded by National Science Foundation Award no. 0540879 , and by the Joint BioEnergy Institute, which is funded by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research , through contract DE-AC02-05CH11231 . F.Z. is supported by the Postdoctoral Fellowships Program of the Natural Sciences and Engineering Research Council of Canada and by the California Institute for Quantitative Biosciences .
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±0.5. g/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±0.5. g/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 - FadR
KW - Fatty acid production
KW - Global regulation
KW - Metabolic engineering
UR - http://www.scopus.com/inward/record.url?scp=84869039746&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2012.08.009
DO - 10.1016/j.ymben.2012.08.009
M3 - Article
C2 - 23026122
AN - SCOPUS:84869039746
SN - 1096-7176
VL - 14
SP - 653
EP - 660
JO - Metabolic Engineering
JF - Metabolic Engineering
IS - 6
ER -