Engineering novel biocatalytic routes for production of semisynthetic opiate drugs.
The morphine alkaloids and their semisynthetic derivatives provide a diverse range of important pharmaceutical drugs. Current production of semisynthetic opiate drugs is by chemical means from naturally occurring morphine, codeine and thebaine. Although various microbial transformations of morphine alkaloids have been identified since the 1960s, more recently there has been considerable effort devoted to engineering biocatalytic routes for producing these important compounds. Such biocatalytic routes are attractive, as they would provide an alternative to the chemical production processes which suffer from limited supply of precursors, often low yields and toxic wastes. The biotransformation of morphine and codeine to the potent analgesic hydromorphone and the mild analgesic/antitussive hydrocodone, respectively, by recombinant Escherichia coli has been demonstrated and the problems encountered when engineering such a system will be discussed.
Boonstra
B
B
Institute of Biotechnology, University of Cambridge, Tennis Court Road, CB2 1QT, Cambridge, UK.
Rathbone
D A
DA
Bruce
N C
NC
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D001709:Biotechnology / Q000379:methods*; D002384:Catalysis; D015195:Drug Design; D004926:Escherichia coli / Q000378:metabolism; D006853:Hydrocodone / Q000031:analogs & derivatives / Q000737:chemistry; D004091:Hydromorphone / Q000031:analogs & derivatives / Q000737:chemistry; D008956:Models, Chemical; D009020:Morphine / Q000138:chemical synthesis / Q000737:chemistry; D009294:Narcotics / Q000138:chemical synthesis* / Q000737:chemistry*; D011994:Recombinant Proteins / Q000378:metabolism
D009294:Narcotics; D011994:Recombinant Proteins; D006853:Hydrocodone; D009020:Morphine; D015067:17-Hydroxysteroid Dehydrogenases; D000429:Alcohol Oxidoreductases; C045221:morphine 6-dehydrogenase; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D004091:Hydromorphone