Hormonal steroids are a class of steroids which are derivatives of androstane, a C19 steroid which has the skeleton structure of gonane (four rings in all-trans configuration) with two additional methyl groups at positions 10P and 13P, respectively (Fig. 6.1). Their biological activity is determined by different hydroxy-and keto-groups, by double bonds at varying positions and also by the presence or absence of a side-chain at the 17P-position. Other classes of steroids, such as bile acids and cardioactive steroid lactones, differ from hormonal steroids by the arrangement of the rings. From these basic structures numerous synthetic analogs are derived with a changed or improved biological activity profile due to the introduction of additional double bonds or substituents.
Steroid hormones regulate essential biological functions in humans and animals, since they act as mineralocorticoids, as glucocorticoids, or as sex hormones. Moreover, many steroid hormone derivatives display anabolic, antihormonal, antiinflammatory, antirheumatic, contraceptive, or sedative activities. Their use as drugs has therefore increased tremendously since 1949 (when Merck first introduced cortisone), and for many decades the overwhelming demand for steroids by the pharmaceutical industry has far exceeded the availability of these compounds from natural sources. Today, steroids represent one of the largest sectors in the pharmaceutical industry with worldwide markets in the region of US$10 billion.
Although the total chemical synthesis of steroids by Woodward and colleagues  constituted a brilliant scientific achievement, it is not economically competitive, so for many decades most steroids have been industrially produced by hemi-synthesis that mainly starts from P-sitosterol (or diosgenin and other phytosterols) and involves a varying number of sophisticated chemical and microbial byconversion steps. Of course, microbial steroid biotransformations must compete with alternative chemical reactions on a cost basis, and with many chemical reactions
being economically feasible, this issue has considerably limited the number of steroid biotransformations that have been actually applied on an industrial scale. Indeed, microbial steps are often circumvented by using more complex chemical reactions provided they can be justified economically. Despite their inherent advantages, microbial reactions also display some specific shortcomings, including the formation of side products, yield variations caused by biological variability due to different batches of cells, and the low solubility of steroids in aqueous solutions.
Recently, the total biosynthesis of steroids from simple carbon sources has been accomplished with genetically engineered yeasts , an achievement that might well constitute a paradigm shift as it opens up the road to chemistry-free steroid production. However, in this chapter we will not focus on pathway engineering but rather concentrate on the different types of single biotransformation reactions that have been performed so far. As the advantages and shortcomings of each biotransformation reaction are discussed, the feasibility of their combination should be borne in mind.
Was this article helpful?