Kwon, Moonhyuk Utomo, Joseph C. Park, Keunwan Pascoe, Cameron A. Chiorean, Sorina Ngo, Iris Pelot, Kyle A. Pan, Cheol-Ho Kim, Seon-Won Zerbe, Philipp Vederas, John C. Ro, Dae-Kyun 2024-01-19T13:01:06Z 2024-01-19T13:01:06Z 2022-04-03 2022-01-07 2155-5435 https://pubs.kist.re.kr/handle/201004/115815 The hallucinogenic plant, Salvia divinorum, synthesizes neoclerodane diterpenes, such as salvinorins, salvidivins, and salvinicins, which are agonistic or antagonistic to mu- or kappa-opioid receptors. From S. divinorum trichomes, crotonolide G synthase (SdCS; CYP76AH39) was identified. It catalyzes the conversion of kolavenol to a dihydrofuran neoclerodane, crotonolide G. O-18(2)-feeding studies confirmed that SdCS incorporates an aerobic oxygen into crotonolide G, rather than forming a cation at C16 that is trapped by the alcohol at C15. Structural modeling of SdCS accompanied by site-directed mutagenesis established the importance of V367 and F479 residues in substrate-binding. The dihydrofuran neoclerodane can serve as a unique lead structure for drug development. English AMER CHEMICAL SOC DITERPENE SALVINORIN SYNTHASE MODULARITY DIVERSITY Cytochrome P450-Catalyzed Biosynthesis of a Dihydrofuran Neoclerodane in Magic Mint (Salvia divinorum) Article 10.1021/acscatal.1c03691 1 ACS CATALYSIS, v.12, no.1, pp.777 - 782 ACS CATALYSIS 12 1 777 782 scie scopus 000737965500001 2-s2.0-85122584384 Chemistry, Physical Chemistry Article DITERPENE SALVINORIN SYNTHASE MODULARITY DIVERSITY biocatalyst cytochrome P450 diterpenoid salvinorin Salvia divinorum