title: Biological production of semisynthetic opiates using genetically engineered bacteria.
abstract: Semisynthetic derivatives of morphine and related alkaloids are in widespread clinical use. Due to the complexity of these molecules, however, chemical transformations are difficult to achieve in high yields. We recently identified the powerful analgesic hydromorphone as an intermediate in the metabolism of morphine by Pseudomonas putida M10. Here we describe the construction of recombinant strains of Escherichia coli that express morphine dehydrogenase and morphinone reductase. These strains are capable of efficiently transforming the naturally occurring alkaloids morphine and codeine to hydromorphone and the antitussive hydrocodone, respectively. Our results demonstrate the potential for recombinant DNA technology to provide biological routes for the synthesis of known and novel semisynthetic opiate drugs.
authors.affiliation: Institute of Biotechnology, University of Cambridge, U.K.
authors.forename: C E
authors.initials: CE
authors.lastname: French
authors.forename: A M
authors.initials: AM
authors.lastname: Hailes
authors.forename: D A
authors.initials: DA
authors.lastname: Rathbone
authors.forename: M T
authors.initials: MT
authors.lastname: Long
authors.forename: D L
authors.initials: DL
authors.lastname: Willey
authors.forename: N C
authors.initials: NC
authors.lastname: Bruce
mesh_terms: D000429:Alcohol Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000701:Analgesics, Opioid / Q000378:metabolism*; D001426:Bacterial Proteins; D003061:Codeine / Q000378:metabolism; D004926:Escherichia coli; D005818:Genetic Engineering; D006853:Hydrocodone / Q000378:metabolism; D004091:Hydromorphone / Q000378:metabolism; D009020:Morphine / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis
chemical_list: D000701:Analgesics, Opioid; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D006853:Hydrocodone; D009020:Morphine; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; C045221:morphine 6-dehydrogenase; C087820:morphinone reductase; D004091:Hydromorphone; D003061:Codeine