Tomita Takeo ,1† Masaya Kobayashi,1† Yuma Karita,2 Yoko Yasuno,2 Tetsuro Shinada,2 Makoto Nishiyama,1 Tomohisa Kuzuyama1*
†Contributed equally.
1Biotechnology Research Center, The University of Tokyo
2Department of Material Science, Graduate School of Science, Osaka City University


We report the three-dimensional structure of cyclolavandulyl diphosphate (CLPP) synthase (CLDS), which consecutively catalyzes the condensation of two molecules of dimethylallyl diphosphate (DMAPP) followed by cyclization to form a cyclic monoterpene, CLPP. The structures of apo-CLDS and CLDS in complex with Tris, pyrophosphate, and Mg2+ ion were refined at 2.00 Å resolution and 1.73 Å resolution, respectively. CLDS adopts a typical fold for cis-prenyl synthases and forms a homo-dimeric structure. An in vitro reaction using a regiospecifically 2H-substituted DMAPP substrate revealed the intramolecular proton transfer mechanism of the CLDS reaction. The CLDS structure and structure-based mutagenesis provide mechanistic insights into this unprecedented terpene synthase. The combination of structural and mechanistic insights advances the knowledge of intricate terpene synthase-catalyzed reactions.

Paper Information

: Angewandte Chemie International Edition
: 10.1002/anie.201708474