298 hapter 9 we would need a multistage reaction and that the desired isomer would only be a small fraction of the final product. We would also be presented with the difficulty of isolating the desired isomer from its isomeric partners. We, therefore, conclud that, although technically feasible, this approach isnot a realistic commercial option. 3)Partial chemical synthesis is perhaps more realistic. If, for example, we wish to lightly modify the structure of a naturally occurring substance, then this might be possible using chemical processes. The problem here is to identify reagents and reactions which will be specific, both in terms of the site of attack on the natural product and the stereospecificity of the reaction Wemust anticipate, therefore, that hemical reactions may be used in some cases, but thisis not a universally applicable strategy 4)The natural systems that produce steroids do so in quantitatively small amounts. Although in principle the cells producing these might be isolated and cultivated in vitro, the quantities produced will still be small and the costs of cultivation are high This approach is, therefore, not generally commercially viable. You may have considered the option of transferring the genes, which encode for the enzymes involved, into an easy to cultivate system(for example a yeast or bacterium) and to ulties in isolating the necessary genes and the multiplicity of the enzyme ste eeded for steroid biosynthesis makes the development costs of this approac extremely high. In the longer term, this may become a realistic option, but is not, tly cially viable 5) The enzymatic transformation of natural products is by far the most attractive option. In this approach, it can be envisaged that sterols, which are relatively abundant, may be selectively modified to produce desired products. The diversity of enzyme activities, their reaction specificity, regiospecificity and stereospecificity areall features which could contribute to carrying out the desired changes. This does not mean, however that transformations using enzyme systems are simple Nevertheless, biotransformations have become of vital importance in the roduction of steroids In the following sections we will explain some applications of enzymes(and cells) in the transformation of sterols and steroids. you should realise however that for each process a decision has to be made whether to use an enzyme-mediated transformation or to use a chemical reaction. In many instances the biotransformation process is the most attractive but, as we will see later, this is not always the case 9.3 Selective degradation of the sterol side chain Re-examine the structures shown in Figure 9.1 and see if you can identify the fundamental difference between sterols and the steroid hormones Although there are many differences between these two groups of molecules, the fundamental difference between them is that the steroids do not possess the long side chain attached to position 17 that occurs in sterols. Thus, if we are to use sterols as the starting point for producing steroids, then we need to selectively remove this side chain298 Chapter 9 we would need a multistage reaction and that the desired isomer would only be a small fraction of the final product We would also be presented with the difficulty of isolating the desired isomer from its isomeric partners. We, therefore, conclude that, although technically feasible, this approach is not a realistic commercial option. 3) Partial chemical synthesis is perhaps more realistic. If, for example, we wish to slightly modify the structure of a naturally OcCuRing substance, then this rmght be possible using chemical processes. The problem here is to identify reagents and reactions which will be specific, both in terms of the site of attack on the natural product and the stereospecificity of the reaction. We must anticipate, therefore, that chemical reactions may be used in some cases, but this is not a universally applicable strategy. 4) The natural systems that produce steroids do so in quantitatively small amounts. Although in principle the cells producing these might be isolated and cultivated in mho, the quantities produced will still be small and the costs of cultivation are high. This approach is, therefore, not generally commercially viable. You may have considered the option of transferring the genes, which ende for the enzymes involved, into an easy to cultivate system (for example a yeast or bacterium) and to control the expression of these genes using strong promoters. Although this approach is theoretically possible using the techniques of genetic engineering, the difficulties in isolating the necessary genes and the multiplicity of the enzyme steps needed for steroid biosynthesis makes the development costs of this approach extremely high. In the longer term, this may become a realistic option, but is not, currently, commercially viable. 5) The enzymatic transformation of natural products is by far the most attractive option. In this approach, it can be envisaged that sterols, which are relatively abundant, may be selectively modified to produce desired products. The diversity of enzyme activities, their reaction specificity, regiospecificity and stereospeaficity are all features which could contribute to carrying out the desired changes. This does not mean, however, that transformations using enzyme systems are simple. Nevertheless, biotransformations have become of vital importance in the production of steroids. In the following sections we will explain some applications of enzymes (and cells) in the transformation of sterols and steroids. You should realise, however, that for each process a decision has to be made whether to use an enzyme-mediated transformation or to use a chemical reaction. In many instances the biotransformation process is the most attractive but, as we will see later, this is not always the case. 9.3 Selective degradation of the sterol side chain Re-examine the structures shown in Figure 9.1 and see if you can identify the n fundamental difference between sterols and the steroid hormones. Although there are many differences between these two groups of molecules, the fundamental difference between them is that the steroids do not possess the long side chain attached to position 17 that occurs in sterols. Thus, if we are to use sterols as the starting point for producing steroids, then we need to selectively remove this side chain