Identification of bottlenecks for P450 biotransformation processes

Cytochrome P450 monooxygenases (P450 or CYP) is a group of heme-containing enzymes hydroxylating non-activated hydrocarbons in a stereospecific manner, something that is hard to achieve via classical chemistry. The importance of these reactions can be stressed by the hydroxylation of steroids, but hydroxylation of e.g. alkanes, alcohols and fatty acids are also highly interesting in e.g. the polymer industry if the processes can be designed with high yield and productivity. The requirement for cofactors, corresponding electron transporting proteins, limited activity and stability of this group of enzymes makes these reactions suitable for whole cell transformations. With the limitations that follow with these requirements it is however a challenging task to reach industrial relevant process targets, especially when it comes to bulk chemicals but also for fine chemicals. Stoichiometric amounts of oxygen and limited water solubility of substrates and products are issues demanding process engineering solutions and if this can be done in parallel with strain development and enzyme engineering it would be optimal. We will present where the current research stands in perspective to an industrial mature P450 biotransformation process identifying the limiting parameters and defining relevant targets.