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1,2-dehydroreticuline synthase

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1,2-dehydroreticuline synthase
Identifiers
EC no. 1.14.19.54
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
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NCBI proteins

1,2-dehydroreticuline synthase (EC 1.14.19.54) and CYP Symbol CYP82Y2 (cytochrome P450, family 82, member Y2), is an enzyme isolated from the opium poppy Papaver somniferum and the field poppy Papaver rhoeas that catalyzes the chemical reaction: [1] [2] [3]

 
 
O2
2 H2O
1,2-dehydroreticuline synthase
 
 
 
 

The three substrates of this enzyme are (S)-reticuline, reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen. Its products are 1,2-dehydroreticulinium cation, oxidised NADP+, and water. The enzyme from field poppy is specific for the (S) enantiomer of reticuline. [1] In the opium poppy, this enzyme forms a fusion protein with 1,2-dehydroreticulinium reductase (NADPH), which immediately converts the reticulinylium cation into {R)-reticuline. The overall result is that (S)-reticuline is converted to {R)-reticuline, which is the precursor of salutaridine, on the pathway to morphine. [4] [5] This gene fusion event has been suggested to evolve only once, about 20 million years ago. [6] [7]

 
 
 
1,2-dehydroreticuline synthase
 
 
 
 
 
 
1,2-dehydroreticuline synthase
 
 
 

The enzyme is a hemoprotein of cytochrome P450 type. [3] [4]

References

  1. 1 2 Enzyme 1.14.19.54 at KEGG Pathway Database.
  2. Hirata, K.; Poeaknapo, C.; Schmidt, J.; Zenk, M. H. (2004). "1,2-Dehydroreticuline synthase, the branch point enzyme opening the morphinan biosynthetic pathway". Phytochemistry. 65 (8): 1039–1046. doi:10.1016/j.phytochem.2004.02.015. PMID   15110683.
  3. 1 2 Farrow, Scott C.; Hagel, Jillian M.; Beaudoin, Guillaume A W.; Burns, Darcy C.; Facchini, Peter J. (2015). "Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy". Nature Chemical Biology. 11 (9): 728–732. doi:10.1038/nchembio.1879. PMID   26147354.
  4. 1 2 Winzer, Thilo; Kern, Marcelo; King, Andrew J.; Larson, Tony R.; Teodor, Roxana I.; Donninger, Samantha L.; Li, Yi; Dowle, Adam A.; Cartwright, Jared; Bates, Rachel; Ashford, David; Thomas, Jerry; Walker, Carol; Bowser, Tim A.; Graham, Ian A. (2015). "Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein". Science. 349 (6245): 309–312. doi:10.1126/science.aab1852. PMID   26113639.
  5. Hawkins, Kristy M.; Smolke, Christina D. (2008). "Production of benzylisoquinoline alkaloids in Saccharomyces cerevisiae". Nature Chemical Biology. 4 (9): 564–573. doi:10.1038/nchembio.105. PMC   2830865 . PMID   18690217.
  6. 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.
  7. Carr, Samuel C.; Rehman, Fasih; Hagel, Jillian M.; Chen, Xue; Ng, Kenneth K. S.; Facchini, Peter J. (2024). "Two ubiquitous aldo-keto reductases in the genus Papaver support a patchwork model for morphine pathway evolution". Communications Biology. 7 (1) 1410. doi: 10.1038/s42003-024-07100-w . PMC   11522673 . PMID   39472466.
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