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Enhancing Fatty Acid Production by Regulation of fadR Expression


Researchers at the 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. 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. JBEIs regulation of fadR expression overcomes these shortcomings. 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 fadRs 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.
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