Thebaine 6-O-demethylase
Thebaine 6-O-demethylase (EC 1.14.11.31, T6ODM) is an enzyme with systematic name thebaine,2-oxoglutarate:oxygen oxidoreductase (6-O-demethylating).[1] It catalyses the following chemical reaction
| Thebaine 6-O-demethylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.14.11.31 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| |||||||||
In the opium poppy Papaver somniferum, this is the first step in one of the two possible pathways to morphine from thebaine. These differ according to which methyl group in thebaine is first to be removed in an oxidation reaction. In this case, it is the one in the C6 position (an enol ether); in the other it is the C3 (phenolic OCH3) which is removed by codeine 3-O-demethylase. Thebaine 6-O-demethylase contains Fe2+ and the methyl group which is removed is converted to formaldehyde, with the oxidation driven by molecular oxygen and α-ketoglutaric acid.[2][3]
The alkaloid product of the reaction, neopinone, can convert spontaneously to the next intermediate, codeinone, in the pathway to morphine via codeine but this step is catalysed in opium poppy by the enzyme neopinone isomerase (NISO).[4][3][5]
Thebaine 6-O-demethylase and codeine 3-O-demethylase are both α-ketoglutarate/Fe(II)-dependent dioxygenases and as of 2024 were the only enzymes confirmed to use this combination for demethylation.[3]
References
- ^ Hagel, Jillian M.; Facchini, Peter J. (2010). "Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy". Nature Chemical Biology. 6 (4): 273–275. doi:10.1038/nchembio.317. PMID 20228795.
- ^ Enzyme 1.14.11.31 at KEGG Pathway Database.
- ^ a b c 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.
- ^ Dastmalchi, Mehran; Chen, Xue; Hagel, Jillian M.; Chang, Limei; Chen, Rongji; Ramasamy, Sukanya; Yeaman, Sam; Facchini, Peter J. (2019). "Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy". Nature Chemical Biology. 15 (4): 384–390. doi:10.1038/S41589-019-0247-0. PMID 30886433.
- ^ Mascavage, Linda M.; Jasmin, Serge; Sonnet, Philip E.; Wilson, Michael; Dalton, David R. (2010). "Alkaloids". Ullmann's Encyclopedia of Industrial Chemistry. pp. 46–54. doi:10.1002/14356007.a01_353.pub2. ISBN 978-3-527-30385-4.
External links
- Thebaine+6-O-demethylase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)