Improving Alkene Reductases for Applications in Asymmetric Synthesis

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With this award, the Chemical Synthesis program is supporting Professor Jon D. Stewart of the Department of Chemistry at the University of Florida to develop new enzyme catalysts for asymmetric conjugated alkene reductions. To date, the overall impact of these enzymes on synthetic chemistry has been modest because the wild-type enzymes accept only a limited range of substrates, provide one possible stereoisomer and lack long-term stability. To overcome these problems, existing flavin-dependent reductase enzymes will be systematically varied at amino acid positions rated most likely to yield improved mutants. X-ray crystallography will be used to understand how substrates bind in the active sites of improved enzymes.The broader impacts involve mentoring high school students (U.F. Precollegiate Training Program), undergraduates (NSF REU), graduate students and postdoctoral researchers, including members of historically underrepresented groups in chemistry. Moreover, the work will provide diverse training in chemistry, x-ray crystallography, molecular biology and biochemistry to these coworkers. In terms of scientific broader impacts, this work is directed at efficient, environmentally benign methods for producing chiral building blocks for medicinal, agrochemical and industrial chemical applications. In addition, the insights gleaned from combining protein engineering, structural studies and catalytic assays will provide new information on flavoproteins, an important class of biocatalysts involved in a diverse set of reactions at the chemistry/biology interface.