Biotransformation of 16-dehydroprogesterone by the intestinal anaerobic bacterium, Eubacterium sp. 144.

Eubacterium sp. 144 biotransformed 16-dehydroprogesterone by initially hydrating approx 50% to 16 alpha-hydroxyprogesterone. The detection of this reaction was dependent, in part, on the solubility state of 16-dehydroprogesterone and was less extensive when the concentration of methanol was insufficient to solubilize the steroid. Cultures containing a mixture of 16-dehydroprogesterone and 16 alpha-hydroxyprogesterone formed isoprogesterone as a final steroid end product. However, the extent of the reductive reaction was influenced by culture age at the time of 16-dehydroprogesterone addition and decreased in older cultures. Moreover, both mid- and late-log phase cells also formed progesterone as a reduced steroid end product. The enzyme(s) responsible for isoprogesterone formation (16-dehydroprogesterone reductase) appeared to be inducible because activity was not evident until 3-6 h after the addition of 16-dehydroprogesterone to early log-phase cultures. Growth inhibitory concentrations of chloramphenicol or rifampin prevented isoprogesterone formation, but not the production of progesterone. At lower concentrations, chloramphenicol delayed both growth and isoprogesterone formation by strain 144. Interestingly, rifampin partially inhibited the 16 alpha-hydroxyprogesterone dehydratase (hydration reaction) in cultures of strain 144, but did not affect the enzyme's activity in cell extracts.