David W. Christianson, University of Pennsylvania

Directing Biosynthesis with Modular Architecture in Terpene Cyclases
Terpene cyclases catalyze the most complex chemical reactions in biology, in that more than half of the carbon atoms in an isoprenoid substrate undergo changes in bonding or hybridization during a multi-step cyclization cascade that proceeds through multiple carbocation intermediates. Although the substrate pool for these enzymes is limited to only a handful of linear isoprenoids, more than 100,000 terpenoid natural products have been identified to date. Crystal structures of terpene cyclases reveal common, modular protein folds that direct unique catalytic strategies underlying this exquisite chemodiversity. Most recently, structural studies of bifunctional assembly-line terpene synthases using cryo-EM and other biophysical techniques show how the first two steps of terpene biosynthesis are combined in nanoscale oligomeric assemblies.