Scott T. Lefurgy
Assistant Professor of Chemistry
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Degrees: PHD, 2007, Columbia Univ; MA, 2005, Columbia Univ; BMUS, 1999, Univ Michigan Ann Arbor; BS, 1999, Univ Michigan Ann Arbor
Isoprenoids are a class of natural products comprised of over 35,000 unique members (including steroids, vitamins, hormones, semiochemicals and defense molecules that are plant secondary metabolites) all of which are based on a common building-block, isopentenyl diphosphate. Many of these compounds have exquisitely potent biological activities, binding to target proteins with nanomolar to micromolar affinity constants, making them excellent candidates for drugs and pesticides. Other isoprenoids have properties similar to diesel fuel and could be burned to power vehicles. Access to isoprenoids on industrial scales is presently limited by the difficulty of stereoselective synthesis and low natural abundance. This problem is compounded when considering synthesis of isoprenoid analogues—compounds with expanded functionality that could hold the key features of novel drugs, biological control agents, or biofuels, but which do not exist in nature and whose syntheses are cumbersome. Our lab addresses this problem from two directions:
1. Mechanistic Enzymology of Isoprenoid Biosynthetic Enzymes from Insect Species
My research group will explore the mechanism of action of the insect and mammalian isoprenoid pathways, which naturally produce isoprenoid analogues, in order to better understand how enzymes could be exploited for synthesis of target molecules. This project involves the expression and purification of the insect pathway enzymes and in vitro characterization of their activities and regulation.
2. Engineering Catalytic Promiscuity into the Mevalonate Pathway for the Production of Isoprenoid Analogues
My research group will expand the chemical repertoire of the existing isoprenoid biosynthetic pathways, through mutation, to efficiently produce analogues of the building-block isopentenyl diphosphate, for the purpose of enzymatically synthesizing isoprenoid analogues of commercial and scientific value. This project involves a systematic generation of enzymes that have been altered by site-directed mutagenesis and the characterization of their activities toward native and non-native substrates. Successful engineered enzymes will be employed to produce gram-scale quantities of isopentenyl diphosphate analogues for downstream applications.