In the last 150 years, humans have synthesized hundreds of thousands of chemicals featuring functional groups not previously found in nature. Many of these chemicals are eventually biodegraded by recently-evolved enzymes and metabolic pathways found within microbes in soil and water. In some cases, microbes metabolize the chemicals incompletely and release new chemicals into the environment. In other cases, microbes completely metabolize the chemicals and assimilate the carbon, nitrogen and/or phosphorous for growth and survival. Due to the large influx of new chemicals over a very short evolutionary time scale, biodegradation is often suboptimal, marked by enzymes that are unstable and inefficient, and metabolic pathways that are incomplete.
In the past, society waited for natural solutions to evolve. A major goal of this proposal is to further develop the ability to routinely and robustly address the limitations of newly evolved enzymes and metabolic pathways and provide new enzymes useful for commercial purposes. The proposed research will result in a protein-engineering framework to help overcome the deficiencies of newly evolved enzyme pathways by combining the accumulated knowledge about biodegradation pathways with state-of-the-art methods in computational enzyme design and laboratory evolution. This research will bring together two different, but complementary, research groups with additional collaborators in quantum chemistry and X-ray crystallography. Overall, we seek to develop a multi-faceted approach for better understanding natural evolution and creating new functions not yet discovered in nature.
The proposed work will train undergraduate, graduate and postdoctoral students at the interface of chemistry, structural biophysics, microbiology, and computer science. Novel pedagogical approaches such as scientific video games and crowdsourcing will be developed and used to engage non-experts in the scientific enterprise. Students from underrepresented groups and minorities will be actively recruited and the PIs will engage in outreach activities involving the public, high school and undergraduate students and their teachers.
