"Microbial production of fuels and chemicals from fatty acids is a greener and sustainable alternative to chemical synthesis," says Zhang, who is the lead author of the Nature Biology paper. "However, high productivities, titers and yields are essential for microbial production of these chemical products to be economically viable, particularly in the cases of biofuels and low-value bulk chemicals."
Hampering microbial production of fatty acid-based chemicals has been metabolic imbalances during product synthesis.
"Expression of pathway genes at too low a level creates bottlenecks in biosynthetic pathways, whereas expression at too high a level diverts cellular resources to the production of unnecessary enzymes or intermediate metabolites that might otherwise be devoted to the desired chemical," Zhang says. "Furthermore, the accumulation of these enzymes and intermediate metabolites can have a toxic effect on the microbes, reducing yield and productivity."
Using the tools of synthetic biology, there have been several strategies developed to meet this challenge but these previous strategies only provide static control of gene expression levels.
"When a gene expression control system is tuned for a particular condition in the bioreactor and the conditions change, the control system will not be able to respond and product synthesis will suffer as a result," Zhang says.
The DSRS responds to the metabolic status of the microbe in the bioreactor during synthesis by sensing key intermediate metabolites in an engineered pathway. The DSRS then regulates the genes that control the production and consumption of these intermediates to allow their delivery at levels and rates that optimize the pathway for maximum productivity as conditions change in the bioreactor.
"Nature has evolved sensors that can be use
|Contact: Lynn Yarris|
DOE/Lawrence Berkeley National Laboratory