Christianson David W
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323, United States.
Curr Opin Chem Biol. 2008 Apr;12(2):141-50. doi: 10.1016/j.cbpa.2007.12.008. Epub 2008 Feb 20.
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.
尽管萜类合酶催化生物学中最复杂的反应，但除了引发离子化以及通过多步反应级联陪伴柔性类异戊二烯底物和碳正离子中间体的构象外，这些酶在催化化学中似乎作用不大。这种化学过程中的保真度和混杂性（即萜类合酶产生一种还是几种产物）取决于活性位点模板在陪伴类异戊二烯偶联或环化反应每一步时的宽容度。对法尼基二磷酸合酶、5-表-马兜铃烯合酶和γ-葎草烯合酶等萜类合酶进行的结构导向诱变研究表明，萜类天然产物的巨大多样性源于所有生命形式中萜类合酶共有的α-螺旋折叠的轻易进化。
