Biotransformation of dehydroepiandrosterone (DHEA) with Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling

Microbial transformation of dehydroepiandrosterone (DHEA, 1) using Penicillium griseopurpureum Smith and Penicillium glabrum (Wehmer) Westling has been investigated. Neither fungi had been examined previously for steroid biotransformation. One novel metabolic product of DHEA (1) transformed with P. griseopurpureum Smith, 15 alpha-hydroxy-17a-oxa-D-homo-androst-4-ene-3,17-dione (5), was reported for the first time. The steroid products were assigned by interpretation of their spectral data such as H-1 NMR, C-13 NMR, IR, and HR-MS spectroscopy. P. griseopurpureum Smith was proven to be remarkably efficient in oxidation of the DHEA (1) into androst-4-en-3,17-dione (2). The strain was also observed to yield different monooxygenases to introduce hydroxyl groups at C-7 alpha, -14 alpha, and -15 alpha positions of steroids. Preference for Baeyer-Villiger oxidation to lactonize D ring and oxidation of the 3 beta-alcohol to the 3-ketone were observed in both incubations. The strain of P. glabrum (Wehmer) Westling catalyzed the steroid 1 to generate both testololactone 3, and D-lactone product with 3 beta-hydroxy-5-en moiety 8. In addition, the strain promoted hydrogenation of the C-5 and C-6 positions, leading to the formation of 3 beta-hydroxy-17a-oxa-D-homo-5 alpha-androstan-3,17-dione (9). The biotransformation pathways of DHEA (1) with P. glabrum (Wehmer) Westling and P. griseopurpureum Smith have been investigated, respectively. Possible metabolic pathways of DHEA (1) were proposed. (C) 2010 Published by Elsevier Inc.