Less Toxic Metabolites, More Chemical Product (http://newscenter.lbl.gov/feature-stories/2013/10/29/less-toxic-metabolites-more-chemical-product/)
The first dynamic regulatory system that prevents the build-up of toxic metabolites in engineered microbes has been reported by a team of researchers with the
Using genome-wide transcriptional analysis, the JBEI researchers identified native regions of DNA - called "promoters" - in E. coli that respond to toxic metabolites by promoting the expression of protective genes. They then developed a system based on these promoters for regulating artificial metabolic pathways engineered into the E.coli to enable the bacterium to produce amorphadiene.
"Static regulators of toxic metabolite levels have been developed but this is the first metabolite regulator that responds to changes in microbial growth and environmental conditions," says
Keasling, who also serves as
From life-saving drugs, such as artemisinin, to sustainable, green biofuels, the metabolic engineering of microbes for the production of valuable chemicals continues to grow in importance. To date, the most productive microbial hosts have been those engineered with heterologous pathways for which they have little or no native regulation of the metabolites being expressed. However, such unregulated expression of heterologous enzymes can be toxic to the host, which can limit the production of the target chemical to well below levels that could be obtained.
"Although synthetic biology has made great strides in creating novel, dynamic genetic circuits, most control systems for heterologous metabolic pathways still rely on inducible or constitutive promoters," Keasling says. "Approaches developed to tailor expression strength by means of promoter libraries, mRNA stability or ribosome-binding are optimized for a particular growth phase or condition in the bioreactor, however, growth and environmental conditions change during the fermentation process."
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