Structure and function of 1-tetrahydrocannabinolic acid (THCA) synthase, the enzyme controlling the psychoactivity of

Shoyama, Yoshinari*; Tamada, Taro; Kurihara, Kazuo; Takeuchi, Ayako*; Taura, Futoshi*; Arai, Shigeki; Blaber, M.*; Shoyama, Yukihiro*; Morimoto, Satoshi*; Kuroki, Ryota

1-tetrahydrocannabinolic acid (THCA) synthase catalyzes the oxidative cyclization of cannabigerolic acid (CBGA) into THCA, the precursor of the primary psychoactive agent 1-tetrahydrocannabinol in . The structure-function relationship of THCA synthase was investigated by X-ray structure determination (2.75 resolution) and mutational analysis. Specific amino acid residues were identified in the active site of THCA synthase that are involved in the oxidative cyclization of the CBGA substrate.