Scientists are increasingly looking for ways to make compounds using biological processes rather than chemical reactions. Such techniques could provide environmentally cleaner ways to manufacture everything from biofuels to drugs, avoiding the harsh solvents and toxic by-products associated with more conventional synthesis. Kristala Jones Prather, an assistant professor of chemical engineering, is developing a promising strategy for synthesizing commercial molecules biologically, from start to finish.
Organic chemists often begin with the structure of a molecule they want to make, then look for the simplest pathway of precursors to produce it. The strategy is called retrosynthesis. Prather believes that biologists can use similar reverse-engineering principles–she calls it “retrobiosynthesis”–to build compounds, stringing natural and engineered enzymes together in novel combinations inside microbial hosts such as E. coli.
“What I’m interested in is designing organisms to be chemical factories,” says Prather, who spent four years in the Bioprocess Research and Development department at Merck. “We used biological systems to do one reaction, and we passed that back to a group of chemists who would do the rest of the fun stuff, and I started thinking, ‘Why can’t biology do more?’”
In 2004, Prather left industry and joined academia so she could help biology do more. Enzymes catalyze a wide range of chemical reactions. Prather is developing a database of these reactions; it includes algorithms that will identify the enzymes most useful for constructing novel metabolic pathways–in many cases leading to chemicals that are not produced through any natural biosynthetic pathway. When multiple enzymes might fit the bill, her software will help select the best one; when no appropriate enzyme is known, the program will help determine which existing enzyme should be modified in order to fill the hole. Prather’s software should be a boon to other synthetic biologists who now construct metabolic pathways by painstakingly combing the literature for possible enzymes, says Jay Keasling, a leading synthetic biologist at the University of California, Berkeley, who supervised her PhD thesis.
Adds John Woodley, professor of chemical engineering at the Technical University of Denmark, “It’s a very clever idea.”