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 U.S. Department of Energy (DOE)'s Joint BioEnergy Institute (JBEI). The JBEI researchers used their system to double the production in Escherichia coli (E. coli) of amorphadiene, a precursor to the premier antimalarial drug artemisinin.
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 Jay Keasling, CEO of JBEI and ranking authority on synthetic biology, who led this research. "Control systems that can sense and respond to environmental or growth changes are needed for the optimal production of a desired chemical."
Keasling, who also serves as Associate Laboratory Director of Biosciences at Lawrence Berkeley National Laboratory (Berkeley Lab), the lead institute in the JBEI partnership, is the corresponding author of a paper describing this research in the journal Nature Biotechnology. The paper is titled "Engineering dynamic pathway regulation using stress-response promoters." Co-authors are Robert Dahl, Fuzhong Zhang, Jorge Alonso-Gutierrez, Edward Baidoo, Tanveer Batth, Alyssa Redding-Johanson, Christopher Petzold, Aindrila Mukhopadhyay, Taek Soon Lee and Paul Adams.
From life-saving drugs, such as artemisinin, to sustainable, green biofuels, the metabolic engineering of microbes for the production of valuable ch
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory