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A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
Discovery of corynanthe synthases in Camptotheca acuminata: medium-chain dehydrogenase/reductase-based gateway to
Van-Hung Bui1, Tuan-Anh Minh Nguyen1, Truc Kim1
1Department of Chemistry, Irving K. Barber Faculty of Science, University of British Columbia, 3247 University Way, Kelowna, BC, Canada.
Main Conclusion:
We combined bioinformatic analysis with in vitro biochemical assays to identify and characterize six medium-chain dehydrogenase/reductase (MDR) enzymes involved in corynanthe alkaloid biosynthesis in Camptotheca acuminata. Camptotheca acuminata, commonly known as the happy tree, is a medicinal plant from the monoterpenoid indole alkaloids (MIAs)-rich Nyssaceae family. In this study, we combined bioinformatic analysis and biochemical investigations to identify new enzymes involved in the biosynthesis of corynanthe alkaloids, an MIA subgroup, in C. acuminata. We identified six medium-chain dehydrogenase/reductase (MDR) enzymes, four of which catalyze the formation of diverse simple corynanthe alkaloids. Structural modeling of the two newly identified enzymes, namely CaMDR1 and CaMDR2, revealed key active-site residues Ser52 and Ser55/His55, crucial for their product profiles. The identification of these new corynanthe synthases further advances our understanding of the formation and diversification of corynanthe alkaloids and MIAs in happy tree and related species.
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