Tailoring biocatalysts by combining protein and cofactor engineering

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#1159434Lutz, StefanEnzymes can be highly effective, selective and sustainable alternatives to chemical catalysts. Nevertheless, their application is often hampered by discrepancies between the functional demands on these biocatalysts in nature versus requirements in laboratory and industrial processes. Protein engineering by rational design and laboratory evolution offers a powerful solution for tailoring enzymes to overcome these differences. Principle investigators Stefan Lutz and Dale Edmondson of Emory University are exploring new engineering strategies for tailoring the catalytic function, substrate specificity and enantioselectivity of flavin-dependent oxidoreductases, an important category of enzymes for asymmetric reduction and oxidation chemistry in biotechnological and pharmaceutical, as well as bioremediation applications. What makes this category of enzymes particularly interesting from a standpoint of protein engineering is their functional complementarity. The protein primarily serves as a scaffold to bind and pre-orient cofactor and substrate(s) while the cofactor is responsible for the chemistry in the active site. By simultaneously remodeling the protein and cofactor, the PIs? approach to generating and assessing many variants offers a unique opportunity to explore synergistic effects that can translate into enzyme redesign and significant enhancements of the functional versatility, catalytic performance and physicochemical properties of existing biocatalysts.The collaborative research project offers opportunity for a highly interdisciplinary training environment for graduate and undergraduate students, as well as provides a framework for outreach involving new curriculum development activities for Atlanta-area high school teachers. Working with the Center for Science Education at Emory and the Georgia Intern-Fellowship for Teachers (GIFT) program, new hands-on experiments on green chemistry and biocatalysis will be developed. The PIs will also continue to participate in Emory's summer undergraduate research experience (SURE) program, working with young scholars from across the southeastern United States, many of them representatives from minorities and underrepresented groups, on new ideas to tweak biocatalysts.