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Enhancing Fatty Acid Production by Regulation of fadR Expression




Researchers at the DOE Joint BioEnergy Institute (JBEI) have developed a genetically modified host cell that increases production of fatty acids and their derivatives. Specifically, the JBEI team found that increased concentration of cellular fadR, a transcriptional factor protein that regulates genes responsible for fatty acid activation and several genes in the fatty acid degradation pathway, lowers fatty acid degradation rate and enhances unsaturated fatty acid biosynthesis, resulting in an increase in total fatty acid production.

Researchers introduced a plasmid that contained the fadR gene under the control of an inducible promoter and measured its effect on fatty acid production. Total fatty acid yield reached 5.2 g/l, six times more than the yield using a previous fatty acid production strain. Results correspond to approximately 75% conversion of the carbon source. Additional testing to understand fadR’s mechanism indicated that fadR increases fatty acid production by changing cells’ overall metabolism rather than acting on one specific gene.

This technology also includes a dynamic sensor-regulator system (DSRS), developed by the researchers to detect metabolic changes in microbes during the production of fatty acid-based fuels or chemicals and control the expression of the specific genes at work to improve production.

Fatty acids are important precursors that can readily be derived to produce biofuels, therapeutic compounds and expensive oils. Synthetic biology has opened the door to fatty acid production from simple carbon sources through engineering microbes such as E. coil or yeast. However, fatty acid yield has been limited, resulting in too high a production cost to be competitive with other methods. The current approach to increasing fatty acid yield is engineering thioesterase enzymes, which are responsible for converting fatty acyl-CoA into fatty acids. But this method has limited success. JBEI’s regulation of fadR expression overcomes these shortcomings.

The Joint BioEnergy Institute (JBEI, is a scientific partnership led by the Lawrence Berkeley National Laboratory and including the Sandia National Laboratories, the University of California campuses of Berkeley and Davis, the Carnegie Institution for Science and the Lawrence Livermore National Laboratory. JBEI’s primary scientific mission is to advance the development of the next generation of biofuels.

DEVELOPMENT STAGE: Proven principle.

STATUS: Published US Patent Application US20130059295 available at Available for licensing or collaborative research.


Zhang, F., Carothers, J.M., Keasling, J. D. “Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids,” Nature Biotechnology, 25 March 2012.

Yarris, Lynn. “New Synthetic Biology Technique Boosts Microbial Production of Diesel Fuel,” Berkeley Lab News Center, March 26, 2012.


Novel Biosynthetic Pathway for Production of Fatty Acid Derived Molecules, EIB-2386



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