Thebaine synthase
| Thebaine synthase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 4.2.99.24 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
Thebaine synthase (EC 4.2.99.24) is an enzyme isolated from the opium poppy, Papaver somniferum, that catalyzes the chemical reaction:[1][2][3]
This is the final step in the biosynthesis of thebaine, forming a 2,3-dihydrofuran ring with loss of a molecule of acetic acid from 7-O-acetylsalutaridinol.[4][5] The reaction occurs spontaneously in alkali but requires catalysis to occur rapidly under physiological conditions near pH 7.[1][6] Thebaine is an intermediate to many other alkaloids including codeine and morphine.[3][7]
The catalytic mechanism of the enzyme has been studied by crystallography. It is a type of SN2 reaction.[8]
References
- ^ a b Enzyme 4.2.99.24 at KEGG Pathway Database.
- ^ Chen, Xue; Hagel, Jillian M.; Chang, Limei; Tucker, Joseph E.; Shiigi, Stacey A.; Yelpaala, Yuora; Chen, Hsiang-Yun; Estrada, Rodrigo; Colbeck, Jeffrey; Enquist-Newman, Maria; Ibáñez, Ana B.; Cottarel, Guillaume; Vidanes, Genevieve M.; Facchini, Peter J. (2018). "A pathogenesis-related 10 protein catalyzes the final step in thebaine biosynthesis". Nature Chemical Biology. 14 (7): 738–743. doi:10.1038/s41589-018-0059-7. PMID 29807982.
- ^ a b Tian, Ya; Kong, Lingzhe; Li, Qi; Wang, Yifan; Wang, Yongmiao; An, Zhoujie; Ma, Yuwei; Tian, Lixia; Duan, Baozhong; Sun, Wei; Gao, Ranran; Chen, Shilin; Xu, Zhichao (2024). "Structural diversity, evolutionary origin, and metabolic engineering of plant specialized benzylisoquinoline alkaloids". Natural Product Reports. 41 (11): 1787–1810. doi:10.1039/d4np00029c. PMID 39360417.
- ^ Vadhel, Agrataben; Bashir, Sabreen; Mir, Ashiq Hussain; Girdhar, Madhuri; Kumar, Deepak; Kumar, Anil; Mohan, Aradhana; Malik, Tabarak; Mohan, Anand (2023). "Opium alkaloids, biosynthesis, pharmacology and association with cancer occurrence". Open Biology. 13 (5) 220355. doi:10.1098/rsob.220355. PMC 10154933. PMID 37132222.
- ^ Muro-Villanueva, Fabiola; Nett, Ryan S. (2025). "Emerging functions within the enzyme families of plant alkaloid biosynthesis". Phytochemistry Reviews. 24 (4): 2463–2484. doi:10.1007/s11101-023-09901-z. PMC 12327836. PMID 40777548.
- ^ Fisinger, Ursula; Grobe, Nadja; Zenk, Meinhart H. (2007). "Thebaine Synthase: A New Enzyme in the Morphine Pathway in Papaver Somniferum". Natural Product Communications. 2 (3) 1934578X0700200305. doi:10.1177/1934578X0700200305.
- ^ Mascavage, Linda M.; Jasmin, Serge; Sonnet, Philip E.; Wilson, Michael; Dalton, David R. (2010). "Alkaloids". Ullmann's Encyclopedia of Industrial Chemistry. pp. 46–53. doi:10.1002/14356007.a01_353.pub2. ISBN 978-3-527-30385-4.
- ^ Chen, Chun-Chi; Xue, Jing; Peng, Wei; Wang, Binju; Zhang, Lilan; Liu, Weidong; Ko, Tzu-Ping; Huang, Jian-Wen; Zhou, Shuyu; Min, Jian; Ma, Lixin; Dai, Longhai; Guo, Rey-Ting; Yu, Xuejing (2020). "Structural insights into thebaine synthase 2 catalysis". Biochemical and Biophysical Research Communications. 529 (2): 156–161. doi:10.1016/J.BBRC.2020.05.199. PMID 32703404.