MIT Engineers Design Genetic Switch that Improves Bacteria’s Productivity

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In Boston, MIT chemical engineers have devised a method of increasing bacterial production of glucaric acid without limiting cell population—a key hurdle to producing commercially relevant quantities of renewable chemicals.

The researchers increased yields by shutting down a competing metabolic pathway, thus increasing available sugar for the desired pathway. While this is not a new approach, halting certain metabolic pathways can impede cell growth—ultimately limiting population and yield. The MIT researchers were able to time the shutdown by engineering cells that produce AHL at different rates. AHL is a protein that at a certain concentration triggers the cell to stop producing enzymes used in the competing pathway. They were then able to identify which strain shut off the competing pathway at the optimal time.

“We can engineer microbial cells to produce many different chemicals from simple sugars, but the cells would rather use those sugars to grow and reproduce. The challenge is to engineer a system where we get enough growth to have a productive microbial ‘chemical factory’ but not so much that we can’t channel enough of the sugars into a pathway to make large quantities of our target molecules,” says Kristala Prather, an associate professor of chemical engineering at MIT and the senior author of the study.

The work was published in Nature Biotechnology,