Microbial Transformation Of Progesterone And16α,17-epoxyprogesterone

Steroids are widely used as anti-inflammatory, anabolic, diuretic, antiandrogenic,progestational, contraceptive and anticancer agents. Hydroxylation of steroids is one ofthe most important reactions in the production of steroid drugs and hormones. Due tothe high regio-and stereo-specificity and environmental compatibility, suchhydroxylation is preferable done by microbial technology. During the past severaldecades, microbial hydroxylation of steroids has been extensively studied, mainly forobtaining new hydroxysteroids with potential pharmaceutical activity as well asrevealing structural specific metabolic behaviour. Many fungi have the ability tohydroxylate steroids in different positions of the gonane core, however only a limitednumber of microbial hydroxylation reported in the scientific literature have actuallybeen applied technically, among them11α-,11β-,16α-and17α-hydroxylation are ofthe highest commercial significance, and7α-,9α,14α-,15α-hydroxylation seem tohave potential industrial exploitation.Progesterone is a sex steroid hormone that plays different physiological roles, beingwell documented its effects on ovulation, establishment and maintenance of pregnancy,as well as its participation in neuronal excitability, neuro-protection, learning andmemory, sleep, immune response, parasitic and viral infections. There were reportsindicated that the11α-OH and the11β-OH derivatives of progesterone are moreeffective than progesterone in stimulating tyrosine phosphorylation，and the14β -hydroxy substituent is an important determinant of activity of the cardiotonic cardiacglycosides and enhances contractility of isolated cardiac muscle.11β-hydroxylation product of16,17α-epoxyprogesterone is an importantintermediate for many anti-inflammatory drugs like hydrocortisone, prednisone acetateand dexamethasone.16,17-epoxyprogesterone, However, very limited knowledge isavailable on the microbial hydroxylation of16α,17-epoxyprogesterone. In presentstudy, the utility of two fungi in progesterone and16α,17-epoxyprogesteronebiotransformation was investigated with the metabolites characterized by variousspectroscopic methods.11β-hydroxylation product of16,17α-epoxyprogesterone is animportant intermediate for many anti-inflammatory drugs like hydrocortisone,prednisone acetate and dexamethasone.16,17-epoxyprogesterone,We then exact thetransformation products of Absidia coerulea from progesterone andepoxyprogesterone,later concentrated it.And these products were identified by themeans of¹H-NMR、¹³C-NMR、IR、MS etc.According to the data,these products are:7β,11α-Dihydroxyprogesterone、7β,15α-Dihydroxyprogesterone、11β,15α-Dihydroxyprogesterone、14β-hydroxyprogesterone、11β-hydroxy-16α，17α-epoxyprogesterone、11β，15α-Dihydroxy-16α,17α-epoxyprogesterone、15β-hydroxy-16α，17α-epoxyprogesterone.At last,conversion of progesterone the condition by Aspergillus coerulea werestudied, the optimal conditions for the transformation.the optimum culture conditionswere: pH6.0, age72h,7%inoculation amount, substrate concentration5g/L. Under theoptimized conditions the conversiontime is shortened, the conversion rate reached at90%..