BIOLOGICAL SYNTHESIS OF THE ANALGESIC HYDROMORPHONE, AN INTERMEDIATE IN THE METABOLISM OF MORPHINE, BY PSEUDOMONAS-PUTIDA M10

The morphine alkaloid hydromorphone (dihydromorphinone) was identified as an intermediary metabolite in the degradation of morphine by Pseudomonas putida M10. A constitutive NADH-dependent morphinone reductase capable of catalyzing the reduction of the 7,8-unsaturated bond of morphinone and codeinone, yielding hydromorphone and hydrocodone, respectively, was shown to be present in cell extracts. The structures have been identified by H-1 nuclear magnetic resonance and mass spectrometry. Morphinone reductase has been partially purified by anion-exchange and gel filtration chromatography. This enzyme has potential applications as a biocatalyst for the synthesis of the highly potent analgesic hydromorphone and the antitussive hydrocodone.