Research abstract
Nature Biotechnology 13, 674 - 676 (1995)
doi:10.1038/nbt0795-674
Biological Production of Semisynthetic Opiates Using Genetically Engineered Bacteria
Christopher E. French1, Anne M. Hailes1, Deborah A. Rathbone1, Marianne T. Long1, David L. Willey2 & Neil C. Bruce1, ,*
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 semi-synthetic opiate drugs.
1Institute of Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QT, U.K.
2Present address: Department of Biochemistry, University of Wales, PO Box 903, Cardiff, CF1 1ST, U.K.
*Corresponding author.