Shelley D. Copley
Ph.D. Harvard University, 1987
Professor; Molecular, Cellular and Developmental Biology
Office: CIRES 241
Biodegradation of recalcitrant pollutants; mechanistic studies of enzymes involved in biodegradation.
Current Research: The Evolutionary Potential of Catalytically Promiscuous Enzymes
Enzymes are superb catalysts, capable of accelerating reactions by up to 17 orders of magnitude. The conditions required to produce and to use enzymes are “green”— they do not require toxic organic solvents or high temperatures and pressures that are costly in terms of energy usage.
New enzymes can emerge from promiscuous activities that arise from the collection of reactive catalytic residues and cofactors at active sites. Although promiscuous activities are normally of no particular use to the organism, they provide an expanded catalytic repertoire from which enzymes may be recruited under novel environmental conditions. However, the potential of promiscuous enzymes goes beyond just catalysis of a single reaction. Promiscuous activities can be assembled into novel combinations to generate what we term “serendipitous” pathways.
We are currently studying three pathways that are patched together from promiscuous enzymes to allow E. coli to bypass a metabolic block. A strain of E. coli lacking erythronate 4-phosphate dehydrogenase cannot grow on glucose because it cannot make the cofactor pyridoxal phosphate. We have identified seven enzymes that, when over-expressed, allow this strain to grow on glucose. Genetic analyses suggest that these enzymes facilitate three serendipitous pathways that allow E. coli to produce a metabolite downstream of the block. We have identified enzymes capable of catalyzing the four steps in one of these pathways (see figure). These pathways illustrate the remarkable evolutionary potential of catalytically promiscuous enzymes residing within the proteome of E. coli, which contains about 2,000 enzymes.
This project will enhance our understanding of the potential for assembling novel metabolic pathways by patching together enzymes that normally serve other functions in the cell. Such pathways could be engineered to allow degradation of anthropogenic chemicals such as pesticides and industrial pollutants, or to allow “green” synthesis of pharmaceuticals, specialty chemicals, and biofuels.
Shelley Copley is a member of the CIRES Professor.