General Overview of presented cascade types

Reaction cascades of groups (1) and (2) will focus on physiologically occurring P450 cascades and have not been yet explored for synthetic appHcations (or only in very few parts). Cascades of groups (3) and (4) describe examples that have been applied for synthetic purposes. Here, examples with isolated enzymes and whole-cell approaches will be discussed. 

A number of kinetic and biochemical studies have been undertaken to elucidate the mechanism of such multistep oxidations. One of the main aspects of these investigations is whether the intermediate product dissociates out of the active site or the subsequent reaction takes place immediately without dissociation of the intermediate. According to this behavior, Guengerich and colleagues [29] distinguish between distributive and processive multistep reactions. 

A membrane reconstitution system was applied to investigate how the presence of CYPllAl affected CYP11B2 activity. Under steady-state reaction conditions, the interaction of CYP11B2 with CYPllAl stimulated the production of corticosterone from deoxycorticosterone but inhibited further reactions from corticosterone to aldosterone. This effect correlates also with the enhanced dissociation of corticosterone from CYP11B2 [34]. 

Another P450 from steroid metabolism, namely CYP17A1, possesses two activities 17a-hydroxylase and 17,20-lyase activity. First, itcatalyzes the 17a-hydroxylation 

Subsequent multistep oxidations catalyzed by one P450 have been found not only within steroid metabolism but also in the degradation ofxenobiotics by mammalian and nonmammalian P450s. 

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