Studies on the microbial transformation of androst-1,4-dien-3,17-dione with Acremonium strictum

Abstract

The strain of Acremonium strictum PTCC 5282 was applied to investigate the biotransformation of androst-1,4-dien-3,17-dione (I; ADD). Microbial products obtained were purified by preparative TLC and the pure metabolites were characterized on the basis of their spectroscopic features (13C NMR, 1H NMR, FTIR, MS) and physical constants (melting points and optical rotations). The 15 alpha-Hydroxyandrost-1,4-dien-3,17-dione (II), 17 beta-hydroxyandrost-1,4-dien-3-one (III), androst-4-en-3,17-dione (IV; AD), 15 alpha-hydroxyandrost-4-en-3,17-dione (V), 15 alpha,17 beta-dihydroxyandrost-1,4-dien-3-one (VI) and testosterone (VII) were produced during this fermentation. Formation of the 15 alpha,17 beta-dihydroxy derivative of ADD is reported for the first time during steroid biotransformation. The bioconversion reactions observed were 1,2-hydrogenation, 15 alpha-hydroxylation and 17-ketone reduction. From the time course profile of this biotransformation, ketone reduction and 1,2-hydrogenation were observed from the first day of fermentation while 15 alpha-hydroxylation occurred from the third day. Optimum concentration of the substrate, which gave the maximum bioconversion efficiency, was 0.5 mg ml(-1) in one batch. The highest yield of the microbial products recorded in this work was achieved within the pH range 6.5-7.3 and at the temperature of 27 degrees C.