Microbiological transformations of delta6a10a-tetrahydrocannabinol.
A screening program was conducted to find microorganisms that catalyze transformation reactions with cannabinoids. Three hundred fifty-eight cultures, consisting of 97 bacteria, 175 actinomycetes, and 86 molds, were incubated in media containing 0.5 mg of Delta(6a,10a)-tetrahydrocannabinol (Delta(6a,10a)-THC) per ml. After 120 h of cultivation, ethyl acetate extracts of the cultures were examined by thin-layer chromatography (TLC) for transformation products. About 18% of the cultures modified Delta(6a,10a)-THC. The ability to modify the substrate did not predominate among any particular group of microorganisms. After purification, the products from three cultures were analyzed by high-resolution mass spectrometry, 100-mHz proton magnetic resonance spectrometry, ultraviolet spectrometry, and infrared spectrometry. These spectral data indicated that a Mycobacterium sp. oxidized Delta(6a,10a)-THC to cannabinol and a diastereomeric pair of 6a-hydroxy-Delta(10,10a)-THC isomers; a Streptomyces sp. and a Bacillus sp. oxidized Delta(6a,10a)-THC to 7-keto-Delta(6a,10a)-THC and 4'-hydroxy-Delta(6a,10a)-THC, respectively. The occurrence of these products and the presence of others that have not yet been isolated or identified indicate that microbial transformation may be a useful tool for the preparation of new cannabinoids that have desirable pharmacological properties.
D000192:Actinomycetales / Q000378:metabolism; D001409:Bacillus cereus / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism; D002186:Cannabinoids / Q000096:biosynthesis; D055598:Chemical Phenomena; D002621:Chemistry; D013759:Dronabinol / Q000378:metabolism*; D005658:Fungi / Q000378:metabolism; D009161:Mycobacterium / Q000378:metabolism*; D009170:Nontuberculous Mycobacteria / Q000378:metabolism*; D010084:Oxidation-Reduction; D013302:Streptomyces / Q000378:metabolism*
D002186:Cannabinoids; D013759:Dronabinol