Figure 1: An overview of the biotransformation of sterols to steroidal pharmaceuticals.
From: Unraveling and engineering the production of 23,24-bisnorcholenic steroids in sterol metabolism
Sterols, including cholesterol and phytosterols, can be degraded to two major valuable intermediates, such as C19 and C22 steroids, through multiple biotransformation steps by some actinomyces, such as Mycobacterium spp. and Rhodococcus spp. Well-studied C19 steroids are AD (androst-4-ene-3,17-dione), ADD (androst-1,4-dien-3,17-dione), 9-OHAD (9α-hydroxy-androst-4-ene-3,17-dione), BD (boldenone) and TS (testosterone). Common C22 steroids are 4-HBC (22-hydroxy-23,24-bisnorchol-4-ene-3-one), 1,4-HBC (22-hydroxy-23,24-bisnorchol-1,4-dien-3-one) and 9-OHHBC (9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one). C22 steroids can be degraded to C19 steroids through multiple undefined biotransformation steps. These two intermediates can be used as ideal precursors to synthesize steroidal pharmaceuticals, such as progestogens and corticosteroids. The abbreviations in red represent the key enzymes that determine product selectivity. KstD, 3-ketosteroid-Δ1-dehydrogenases; KSH, 3-ketosteroid-9α-hydroxylases; Hsd4A, a short chain dehydrogenase. Arrows in arrays signify multiple biotransformation steps. Curved arrows indicate the application value of C22 steroids and C19 steroids to produce steroidal pharmaceuticals. The dashed arrow indicates undefined biotransformation steps.
