Flexibility of the endogenous progesterone lactonisation pathway in Aspergillus tamarii KITA: transformation of a series of cortical steroid analogues.

A range of cortical steroids have been transformed by the fungus Aspergillus tamarii, which has the ability to convert progesterone to testololactone in high yield through a four step enzymatic pathway. 16alpha,17alpha-Epoxyprogesterone underwent a rare epoxide opening resulting in a unique inversion of stereochemistry to give 16beta-hydroxy-17alpha-oxa-D-homo-androst-4-en-3,17-dione. The metabolism of deoxycorticosterone resulted in relatively efficient transformation to testololactone with no other products isolated. Transformation of 17alpha-hydroxyprogesterone yielded 17alpha-oxa-D-homo-androst-1,4-dien-3,17-dione, a lactone not previously isolated from A. tamarii. Cortexolone was transformed to the 20(R)-alcohol with no further transformation observed. Evidence is also presented for the presence of a highly flexible but stereospecific keto-reductase. All metabolites were isolated by column chromatography and were identified by 1H, 13C NMR, DEPT analysis and other spectroscopic data.