Biological Production of Semisynthetic Opiates Using Genetically Engineered Bacteria

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 metab...

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Bibliographic Details
Published in:Bio/Technology 1995-07, Vol.13 (7), p.674-676
Main Authors: French, Christopher E, Hailes, Anne M, Rathbone, Deborah A, Long, Marianne T, Willey, David L, Bruce, Neil C
Format: Article
Language:English
Subjects:
Agriculture
Alcohol Oxidoreductases - biosynthesis
Alcohol Oxidoreductases - genetics
Analgesics, Opioid - metabolism
Bacterial Proteins
Bioinformatics
Biological and medical sciences
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Codeine - metabolism
Escherichia coli
Fundamental and applied biological sciences. Psychology
Genetic Engineering
Health. Pharmaceutical industry
Hydrocodone - metabolism
Hydromorphone - metabolism
Industrial applications and implications. Economical aspects
Life Sciences
Morphine - metabolism
Other active biomolecules
Oxidoreductases - biosynthesis
Oxidoreductases - genetics
Plasmids - genetics
Production of active biomolecules
Pseudomonas putida
Recombinant Proteins - biosynthesis
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Summary: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 semi-synthetic opiate drugs.
ISSN:0733-222X
1087-0156
2331-3684
1546-1696
DOI:10.1038/nbt0795-674