It’s been several decades since chemical engineers first used microbes as miniscule chemical factories. Kristala Jones Prather now hopes to boost production to the next level, generating substances such as tumor-fighting drugs and food additives in more efficient ways.
Prather, professor of chemical engineering, has come up with genetic devices she calls metabolite valves, which redirect metabolism-related molecules from their primary purpose—supporting cell growth—to helping the cell manufacture useful chemicals and specialty compounds.
Since scientists found they could genetically tweak cells to churn out important substances such as insulin, the race has been on to make cells produce more with less. For some compounds, the goal is to improve on the microbes’ natural mode of production. Others necessitate that the microbes perform in ways not found in nature. Prather’s lab created a specially engineered strain of the common bacteria E. coli that synthesizes substances it would not normally produce, such as the flavorant vanillin, and a compound related to the pharmaceutical ephedrine, used as a stimulant, decongestant, and appetite suppressant.
After earning a bachelor of science from MIT, Prather went on to a PhD program at the University of California at Berkeley and then a four-year stint in R&D at drug powerhouse Merck, both of which furthered her fascination with biology as a tool for chemical engineering. At Merck, Prather used bacterial enzymes to catalyze a chemical reaction. The method turned out to be more efficient than the traditional chemical factory approach, making her wonder if she could fine-tune cell metabolism pathways even further in the hope of coming up with new and improved methods of chemical synthesis.
Prather, who joined the MIT faculty in 2004, continues to pursue her goal of having the field reach new milestones. “I would love to see more bio-based products making it to market,” she said. “I would also like to see more novel organisms being employed for chemical synthesis, both at the academic and industrial scales.”
Prather is exploring ways to tweak different pathways within the cell. Instead of knocking out genes that might be necessary for cell health and growth, she modulates enzyme levels that allow host cells to switch between growth and production modes. Her metabolite valve strategy works well to generate glucaric acid, an ingredient in health supplements, detergents, and road deicers.
“With our valves, we’re able to regulate substrate usage between cell growth and product formation. This approach can improve yield of a product in E. Coli twofold: a similar system engineered in yeast leads to improvement in product yields of about fiftyfold,” she says. “We’re very excited to continue applying this approach to other systems. We certainly want to push more of our work towards commercial relevance.”
Prather is particularly excited by the idea that one day, “we may view biological synthesis of chemical compounds in much the same way that we think of synthetic organic chemistry—expanding the toolbox of chemical transformations that can be used to solve problems and change lives.”