Codeine reductase

Keywords chemotaxonomy patchy distribution biosynthesis genes horizontal gene transfer endophytes evolution tryptophan decarboxylase tyrosine decarboxylase phenylalanine ammonia-lyase chalcone synthase strictosidine synthase berberine bridge enzyme codeine reductase... 

The isolation of the cDNAs encoding the enzymes involved in diverse isoquinoline alkaloid formation in plants and microorganisms allowed the first metabolic engineering routes to be developed and paved the way for new ways of future production of isoquinoline alkaloids. For instance, transgenic opium poppy plants were created in which codeinone reductase was suppressed by RNAi, resulting in the substitution of morphine synthesis with the non-narcotic precursor reticuline [110]. In a similar approach, RNAi suppression or overexpression of salutaridinol 1-0-acetyltransferase in opium poppy led to accumulation of salutaridine or increase of morphine, codeine and thebaine content [111], suppression of the BBE led to accumulation of berberine in California poppy cells [112],... 

As shown in Scheme 13.43, the conversion of thebaine to codeine and thence to morphine is effected by enzymes that have not yet been completely characterized. It is clear that methyl groups must be removed and a reduction [codeinone reductase, EC 1.1.1.247, NAD(P)H NAD(P)] must be effected. The sequence is not clear, although there does seem to be a general consensus that the scheme shown probably applies. 

E4 Codeine-O-demethylase E5 Thebaine 6-0-demethylase E6 Codeinone reductase... 

---