Salutaridine synthase

Conversion of (S)-reticuline to its ( )-epimer is the first committed step in morphinan alkaloid biosynthesis in certain species. 1,2-Dehydroreticuline reductase catalyzes the stereospecific reduction of 1,2-dehydroreticuline to (7 )-reticuline.39 Intramolecular carbon-carbon phenol coupling of (if)-reticuline by the P450-dependent enzyme salutaridine synthase (STS) results in the formation of salutaridine.40 The cytosolic enzyme, salutaridine NADPH 7-oxidoreductase (SOR), found in Papaver bracteatum and P. somniferum, reduces salutaridine to (7S)-salutaridinol.41 Conversion of (7S)-salutaridinol into thebaine requires closure of an oxide bridge between C-4 and C-5 by acetyl coenzyme A salutaridinol-7-0-acetyltransferase (SAT). The enzyme was purified from opium poppy cultures and the corresponding gene recently isolated (Fig.7.2).42,43 In the last steps of morphine... 

Figure 2.8 Biosynthesis of morphine via the conversion of (S)-reticuline to (R)-reticuline, salutaridine and thebaine. SalS, salutaridine synthase SaIR, salutaridine reductase THS, thebaine synthase COR, codeinone reductase.

Figure 2 Established enzymatic formation of Thebaine from (fl)-Reticuline in the poppy (Papaver somnifemm). The participating enzymes are 1 =salutaridine synthase 2 = NADPH-de-pendent salutaridine oxidoreductase Sssalutaridinol 7-O-ace-tyltransferase.

Gesell, A., et al, CYP719B1 is salutaridine synthase, the C-C phenol -coupling enzyme of morphine biosynthesis in opium poppy. J. Biol Chem., 2009. 284(36) p. 24432-42. 

It is then argued (Scheme 13.42) that (f )-reticuline undergoes oxidation to a diradical, which couples intramolecularly to yield salutaridine.The coupling process is catalyzed by salutaridine synthase (EC 1.14.21.4) and, in the process, nicotinamide adenine dinucleotide [NAD(P)H] is oxidized to NADP" and oxygen is converted to water. Then, use of another equivalent of nicotinamide adenine dinucleotide [NAD(P)H NAD(P)" ] as a cofactor for salutaridine reductase (EC 1.1.1.248) is used to effect reduction of salutaridine to salutaridinol. 

Enzyme 1.14.21.4 salutaridine synthase (R)-reticuline oxidase (C-C phenol-... 

Reticuline is a chemical compound that can be found in Lindera aggregata. It is also one of the alkaloids found in opium. Metabolism showed that 3 -hydroxy-A -methyl-(S)-coclaurine 4 -0-methyltransferase uses 5-adenosyl methionine and 3 -hydroxy-A -methyl-(S)-coclaurine to produce S-adenosylhomocysteine and (S)-reticuline. Reticuline oxidase uses (S)-reticuline and O2 to produce (S)-scoulerine and H2O2. Salutaridine synthase uses (R)-reticuline, NADPH, H", and O2 to produce salutaridine, NADP", and H2O. 1,2-dehydroreticulinium reductase (NADPH) uses (R)-reticuline and NADP + to produce 1,2-dehydroreticulinium, NADPH, and H". ... 

Salutaridine is an alkaloid that is present in the tnorphinan alkaloid pathway of opium poppy. Its precursor is the alkaloid (R)-reticuline. (R)-reticuline is converted to salutaridine by the enzyme salutaridine synthase. Salutaridine is converted to salutaridinol by the enzyme salutaridine reductase (SalR), with the reduction of NADPH to NADP+. 

Fig. 4 Pathways of benzylisoquinoline biosynthesis. A selection of biosynthetic enzymes is notified with their localization in the cytosol (yellow), the ER membrane (red) or in the lumen of cytosolic vesicles (blue). Informations are taken mainly from Facchini and St-Pierre (2005), Bock et al. (2002), own experiments and other references cited in the text. BBE, berberine bridge enzyme CFS, cheilanthifoline synthase CNMT, coclaurine N-methyltransferase COR, codeinone reductase DBOX, dihydrobenzophen-anthridine oxidase MSH, N-methylstylopine 14-hydroxylase NCS, norcoclaurine synthase NMCH, N-methylcoclaurme 3 -hydroxylase 4 OMT, 3 -hydroxy-N-methylcoclaurine 4 -0-methyltransferase 60MT, norcoclaurine 6-O-methyltransferase 70MT, reticuline 7-O-methyltransferase P6H, protopine 6-hydroxylase SAT, salutaridinol-7-O-acetyltransferase SOR, salutaridineiNADPH 7-oxidoreductase STS, stylopine synthase SAS, salutaridine synthase TNMT, tetrahydroprotoberberine cis-N-methyltrans-ferase TYDC, tyrosine decarboxylase CAS, canadine sjmthase SOMT, scoulerine 9-O-methyltransferase STOX, (S)-tetrahydroprotoberberine oxidase...

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