Bioconversion Of 17α-mehyl-testosterone For Preparation Of Methandienone With Arthrobacter Simplex

Comparing with chemical synthesis methods, the transformation of steroids by microbiological methods is of more considerable commercial interest in the production of pharmaceutical steroids After dehydrogenation and double bond formation in C_1,2 of steroid A ring, the anti-inflammatory activity of hormone type medicines will be many times higher than that of the original one. At the mild conditions (such as low temperature, low pressure, etc.), the dehydrogenation of steroid can be catalyzed by certain microorganisms with higher selectivity and productivity.Dehydro-17α- methyltestosterone(methandienone)is one of anabolic steroids. Comparing with 17α-methyltestosterone, Methandienone is of higher activity.The current status of steroids industry, the progress and the applications in micro-dehydrogenation of steroid were reviewed, and the prospects of steroid medicines were discussed as well. Based on the only a few reports on the bio-dehydrogenation of 17α-methyltestosterone and low conversion ratio of 17α-methyltestosterone currently, the purposes of this work are: the strain screening, better fermentation conditions for methandienone and the methods of separation and purification from the fermentations.A strain 31-2-50 with higher bioconversion ratio of 17α-methyltestosterone was screened out by bioconversion tests in shake bottle after separation and purification from 3 strains of A.simplex.The bioconversion of 17α-methyl-testosterone to methandienone was carried out by Arthrobacter simplex. This conversion was influenced significantly by the composition of the cultivation medium. A medium composed of (g/L): Glucose, 10;corn liquid, 12;yeast extract, 5;KH₂PO₄ , 2.5;supported relatively high methandienone products. The biotransformation conditions for the dehydrogenation of 17α-methyltestosterone were also investigated in depth, and the optimal conditions were obtained as follows: 5% of inoculum volume, initial pH value of medium, pH 6.4, and a large number of product crystals were existed in the medium and the conversion rate of around 70% was further accelerated when the substrates added to the medium were dispersed by the hydrophilic solvent.Based on the experiments of above, the fermentation parameters of 7L fermentor were established. All of these will be benefitial for the further industrial works.