Biosynthetically-patterned Biotransformations

It is possible to distinguish between two major types of biotransformation. On the one hand, there are xenobiotic transformations in which the substrate is completely alien to the microorganism whilst, on the other hand, there are biosynthetically-patterned biotransformations in which the substrate bears a formal relationship to an intermediate of one of the natural biosynthetic pathways that the organism possesses. 

Whilst these biosynthetically-patterned biotransformations of terpenoids have been described in the context of studies with G. fujikuroi, studies with other fungi have shown that a similar pattern of results can be obtained using other biosyntheses. Although the yields of the metabolites are often poor, the transformations do have some value in the preparation of rare or labelled compounds. Furthermore, the results reveal some constraints on the biosynthetic pathways and provide information on the stereo-electronic requirements of enzymatic processes that could not be obtained from conventional studies. 

Biosynthetically-patterned microbiological transformations exploit the substrate flexibility of enzymes involved in the biosynthesis of secondary metabohtes. These biotransformations are sometimes known as analogue biosynthesis or precursor-directed biosynthesis. This approach to biotransformation can be useful in preparing analogues of biologically-active microbial metabolites for structure-activity studies, a feature that has been exploited with penicillins using a cloned isopenicillin N synthase. The structures of the substances that are transformed and of their products can also shed light on the stereo-electronic constraints of enzymatic steps and on the nature of biosynthetic intermediates, a feature that has been exploited in studies on the cyclization of squalene to the triterpenes and steroids. 

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