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The chemical diversity found in plants has served as a major source of inspiration to many synthetic and biological chemists. Nature has evolved enzyme active sites to catalyze the synthesis of structurally complex compounds that serve as pharmaceuticals, insecticides, dyes, perfumes, and biofuels. In Catharanthus roseus, approximately 130 structurally complex monoterpene indole alkaloids are produced, including the clinically used anti-mitotic drugs, vinblastine and vincristine. The common intermediate to all monoterpene indole alkaloids is strictosidine, the product of an asymmetric Pictet-Spengler condensation of tryptamine and the iridoid monoterpene secologanin. This reaction is catalyzed by the enzyme strictosidine synthase. This thesis describes the use of kinetic isotope effects, the rate dependence on pH, as well as structural and computational data to propose a mechanism by which strictosidine synthase catalyzes the Pictet-Spengler reaction. Notably, the data also shed light on the mechanism of th