Steroid hormones microbial transformation

Combined use of microbial enzymes as biocatalysts with chemical synthesis has its origin in the steroid transformation developed in the USA in the early 1950s. Arima and his group [11] invented a unique microbial conversion process, in which the aliphatic side-chain of cholesterol was cleaved to produce a steroid core as a starting material for chemical synthesis of steroid hormones. Yamada et al. discovered the reverse reaction of the pyridoxal-containing L-amino acid lyases and applied them to synthesize L-tryptophan and l-DOPA [12] from pyruvate, ammonia and corresponding aromatic compounds. Since these early achievements, a variety of unique processes with newly screened microbial enzymes as biocatalysts have been invented. 

The most important chapter in the history of microbial transformations of steroids has had to do with the synthesis of the hormones of the adrenal gland and of their more powerful and therapeutically selective synthetic analogs. Studies of the composition of steroids in bovine and other mammalian adrenal glands by Kendall, Reichstein, and Wintersteiner, and their respective collaborators, begun in the early 1930 s, led eventually to the isolation, characterization, and structural proof of cortisone (1938). 

The synthesis of adrenal steroids and major excreted metabolites is illustrated in Fig. 5.3.1. Little secreted steroid product is excreted unchanged and most of the catabolism takes place in the liver, although cortisol metabolism by the kidney is clinically important and microbial metabolism in the gut can be quantitatively significant. The major metabolic transformations of hormonal steroids and precursors are detailed by Makin [54] and summarized in Fig. 5.3.2. GC-MS steroid profiling is the technique of choice for measurement of important urinary constituents. 

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