Alternative substrates for chain elongation enzymes

ORGN 643

Nicole A. Heaps, nicoleh@chem.utah.edu, Department of Chemistry, University of Utah, 315 S 1400 E, Salt Lake City, UT 84112 and C. Dale Poulter, poulter@chem.utah.edu, Department of Chemisty, University of Utah, 315 South 1400 East, Salt Lake City, UT 84112.
Isopentenyl diphosphate isomerase (IDI) interconverts IPP to the allylic isomer DMAPP. There are two known isomerase enzymes, type I and type II. The mechanism of type I is an antarafacial addition/elimination mechanism which is postulated to involve a carbocationic intermediate. The mechanism of the type II enzyme has yet to be discovered. Both IPP and DMAPP are required for the major building reactions in the isoprenoid biosynthetic pathway. These reactions are catalyzed by chain elongation enzymes, the best studied of these enzymes is farnesyl diphosphate synthase. The mechanism is an ionization-condensation-elimination mechanism. Utilizing structural and mechanistic studies of both chain elongation and isomerase enzymes we have designed a set of alternate substrates. The substrate analogs are designed to stabilize the formation of a carbocation, and will be employed for the production of novel isoprenoid compounds as well as for further mechanistic and structural studies.