Cytochrome P450-Catalyzed Biosynthesis of a Dihydrofuran Neoclerodane in Magic Mint (Salvia divinorum)
Cytochrome P450-Catalyzed Biosynthesis of a Dihydrofuran Neoclerodane in Magic Mint (Salvia divinorum)
复制标题
DOI：
10.1021/acscatal.1c03691
复制
发表时间：
2021-12-28
期刊：
影响因子：
12.9
通讯作者：
Ro, Dae-Kyun
中科院分区：
文献类型：
--
作者：
Kwon, Moonhyuk;Utomo, Joseph C.;Ro, Dae-Kyun
致幻植物鼠尾草（Salvia divinorum）合成新克罗烷二萜，如鼠尾草素（salvinorins）、鼠尾草素（salvidivins）和鼠尾草素（salvinicins），其对μ-或κ-阿片受体具有激动或拮抗作用。来自酿脓链球菌divinorum毛状体，巴豆酸G合酶（SdCS; CYP 76 AH 39）进行了鉴定。它催化kolavenol转化为二氢呋喃新克罗烷，crotonoprotein G。O-18（2）-喂养研究证实，SdCS将需氧氧结合到巴豆酸G中，而不是在C16处形成被C15处的醇捕获的阳离子。伴随定点诱变的SdCS的结构建模确立了V367和F479残基在底物结合中的重要性。二氢呋喃新克罗烷可作为药物开发的独特先导结构。
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.