Unearthing the roots of the terpenome.
Although terpenoid synthases catalyze the most complex reactions in biology, these enzymes appear to play little role in the chemistry of catalysis other than to trigger the ionization and chaperone the conformation of flexible isoprenoid substrates and carbocation intermediates through multistep reaction cascades. Fidelity and promiscuity in this chemistry (whether a terpenoid synthase generates one or several products), depends on the permissiveness of the active site template in chaperoning each step of an isoprenoid coupling or cyclization reaction. Structure-guided mutagenesis studies of terpenoid synthases such as farnesyl diphosphate synthase, 5-epi-aristolochene synthase, and gamma-humulene synthase suggest that the vast diversity of terpenoid natural products is rooted in the facile evolution of alpha-helical folds shared by terpenoid synthases in all forms of life.
Christianson
David W
DW
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, United States. chris@sas.upenn.edu
D019883:Alkyl and Aryl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003500:Cyclization; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D013729:Terpenes / Q000378:metabolism*
D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C108877:terpene synthase