Chemistry Seminar: Promiscuity, serendipity and metabolic innovation

Promiscuity, serendipity and metabolic innovation

Dr. Shelly Copley
Professor of Molecular, Cellular, and Developmental Biology
University of Colorado, Boulder

Dr. Copley will discuss her research on using laboratory evolution to explore the restoration of PLP production in E.Coli via patchwork assembly of a four-step bypass pathway comprised of promiscuous activities of enzymes that normally serve other functions.

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Abstract:
Bioinformatic evidence suggests that metabolic pathways have evolved by “patchwork” recruitment of enzymes that have a promiscuous ability to catalyze newly important reactions. However, we cannot explain why certain pathways arose rather than the thousands of other possibilities. Further, we have little insight into the process by which novel pathways were patched together and flux was improved via mutations. We are using laboratory evolution to address this question. We have deleted the gene encoding PdxB (4-phosphoerythronate dehydrogenase), an enzyme in the pathway for synthesis of the essential cofactor pyridoxal 5’-phosphate (PLP), in E. coli. We evolved several strains of this ∆pdxB mutant. PLP levels were returned to normal within only 150 generations. PLP synthesis was restored by patchwork assembly of a four-step bypass pathway comprised of promiscuous activities of enzymes that normally serve other functions. We have identified why mutations enabled assembly of the novel pathway. This work provides new insights into the early stages of evolution of a new metabolic pathway.

Speaker Bio:
Dr. Shelley D. Copley is Professor of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder. She took her A.B. Degree (summa cum laude) in Biochemistry from Harvard in 1980 and her Ph.D. in Biophysics from Harvard University in 1987. Joining the faculty at the University of Colorado at Boulder in 1990, she is also a Fellow of the Cooperative Institute for Research in Environmental Sciences at the University. Dr. Copley is the author of more than 75 publications dealing with the evolution of enzymes and metabolic pathways in the context of the complex metabolic and regulatory networks in cells. In her laboratory the evolutionary potential of promiscuous activities at the molecular level is being investigated. Although promiscuous activities are inefficient, they are often orders of magnitude faster than un-catalyzed reactions. Thus, a promiscuous activity provides an excellent starting place for evolution of a new enzyme if that activity becomes important for growth or survival.

Intended Audience:
All are welcome.
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