短刺小克银汉霉菌对维拉帕米转化的能力

目的　研究微生物模型对药物维拉帕米的代谢转化能力 ,并与人体内药物代谢进行比较。方法通过菌株筛选 ,确定以短刺小克银汉霉菌AS 3.15 3为转化菌株 ,采用液相色谱 质谱联用技术对代谢产物进行检测 ,并考察了微生物转化体系中影响代谢物产率的主要因素。结果　该霉菌转化维拉帕米形成C -N键和C -O键断裂的 10种氧化代谢产物。发现以pH 6 .5 ,底物浓度 0 .0 75 % ,转化反应持续 96h等条件 ,代谢产物的总产率 >95 % ,其中 1种主要产物N 去短链烷基维拉帕米的产率 >6 5 %。结论短刺小克银汉霉菌AS 3.15 3对维拉帕米具有与人体类似而且广泛的代谢途径 ,是研究人体药物代谢适宜的体外模型

Capability of Cunninghamella blakesleana to transform verapamil

AIM To study the potential of microorganism to metabolize verapamil and the similarities between humans and microbial drug metabolism. METHODS Among 13 microorganism species screened, Cunninghamella blakesleana AS 3.153 was selected to biotransform verapamil for further study. Metabolites produced by the fungus were identified by liquid chromatography-tandem mass spectrometry (LC-MS n). Factors influencing biotransformation were investigated. RESULTS Based on the data of LC-MS n, it can be inferred that the major products of verapamil transformed by Cunninghamella blakesleana AS 3.153 were mainly via cleavage of C-N or C-O bonds. Ten metabolites were identified. The influential factor experiments showed that when pH 6.5, 0.075% of substrate concentration and 96 h of incubation, the total yield was >95% and the yield of the major metabolite, N-dealkylverapamil, was >65%. CONCLUSION There were diverse pathways for Cunninghamella blakesleana AS 3.153 to metabolize verapamil, which were similar to humans, so it may be used as a model of mammalian drug metabolism.