1,2-dehydroreticulinium reductase (NADPH)

1,2-dehydroreticulinium reductase (NADPH)
Identifiers
EC no.1.5.1.27
CAS no.130590-58-8
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO
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PMCarticles
PubMedarticles
NCBIproteins

1,2-dehydroreticulinium reductase (NADPH) (EC 1.5.1.27) is an enzyme that catalyzes the chemical reaction

reticulinylium cation
 
 
H+
 
 
 
 
 

The three substrates of this enzyme are 1,2-dehydroreticulinium cation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) and a proton. Its products are (R)-reticuline and oxidised NADP+. The enzyme does not catalyse the reverse (oxidation) reaction.[1][2]

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (R)-reticuline:NADP+ oxidoreductase. This enzyme is also called 1,2-dehydroreticulinium ion reductase. It participates in morphinan alkaloid biosynthesis.[1]

In the opium poppy, Papaver somniferum, this enzyme forms a fusion protein with 1,2-dehydroreticuline synthase, which converts (S)-reticuline to reticulinylium cation. The overall result is that the (S) enantiomer of reticuline is converted to {R)-reticuline, which is the precursor of salutaridine, on the pathway to morphine.[3] This gene fusion event has been suggested to evolve only once, about 20 million years ago.[4][5]

 
 
 
 
 
 
 
 
 
 
 
 

References

  1. ^ a b Enzyme 1.5.1.27 at KEGG Pathway Database.
  2. ^ De-Eknamkul W, Zenk MH (1992). "Purification and properties of 1,2-dehydroreticulinium reductase from Papaver somniferum seedlings". Phytochemistry. 31 (3): 813–821. Bibcode:1992PChem..31..813D. doi:10.1016/0031-9422(92)80020-F.
  3. ^ 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.
  4. ^ Tian Y, Kong L, Li Q, Wang Y, Wang Y, An Z, Ma Y, Tian L, Duan B, Sun W, Gao R, Chen S, Xu Z (November 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.
  5. ^ 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.