Cell-Free Synthesis of Cannabistilbene I: A Dual Acting Anti-Inflammatory from Cannabis sativa

Abstract Despite the potential of Cannabis bibenzyls to remedy acute and chronic inflammation, their relative scarcity, in planta, has hindered applications for them in mainstream therapeutic efforts. Here, we describe the biocatalytic synthesis of cannabistilbene I (1), a prototypical Cannabis bibenzyl, and demonstrate its utility as an anti-inflammatory agent. A Cannabis O-methyltransferase (CsOMT1) was first identified that catalyzes the 3-hydroxymethylation of dihydroresveratrol (2) to produce pinobistilbene (3). Structural characterization of CsOMT1 revealed that the substrate-binding pocket requires the ethyl bridge