CAREER: Evolutionary Mechanisms for Recruiting Promiscuous Enzyme Activities into New Metabolic Pathways

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The scientific goal of this project is to discover how and why certain enzymes are capable of evolving new functions. Previous research partially answered the "how" question: in addition to their biological function, many enzymes carry out "promiscuous" side reactions by chance. If a promiscuous activity becomes useful for an organism, natural selection will act to improve that activity. Although many enzymes have promiscuous activities, they might not be equally capable of evolving new functions. In order to identify characteristics that promote evolvability, this research project is comparing the evolution, structure, and function of a family of promiscuous enzymes to their non-promiscuous relatives. Identifying the sequence, structural, and catalytic properties that were required for the evolution of a new function will facilitate the development of new strategies for engineering other enzymes to carry out new activities. Improving protein engineering methodology has numerous applications in industry and medicine, such as using biodegradable enzymes to replace toxic chemicals in industrial processes.Broader ImpactsThis project will support education in the research laboratory and classroom, providing interdisciplinary training in bioinformatics and biochemistry, a major growth area in the biological sciences because of the development of high-throughput DNA sequencing technologies. The participation of under-represented minorities in scientific research will be increased by providing full-time summer internships to undergraduates recruited from colleges that mainly serve minority populations and have limited research opportunities. Active learning will be fostered through the augmentation of a lecture course with a research project that integrates concepts from metabolism with bioinformatics methods developed in the research laboratory. Finally, evolutionary thinking will be introduced into a freshman biochemistry and genetics class, with the goal that these students will become citizens who can explain the mechanisms of evolution and how it impacts their lives.