Modelling of the Baeyer-Villiger Monooxygenase Catalysed Synthesis of Optically Pure Lactones

Abstract

While considerable progress has been made on the implementation of biocatalytic hydrolyses, there are still a number of engineering issues to address regarding the implementation of biocatalytic redox and carbon-carbon bond forming reactions. The use of process models linked to graphical tools (process maps) to describe the parameter boundaries for effective reactor operation have found particular use for these classes. Such process maps help to describe the properties of the biocatalyst and also the properties of the reactants and products which are frequently labile in the reactor environment. Data to form and verify such models can be rapidly collected at the microwell-scale. The models themselves can either be mechanistic or, as used here, based on experimental data. The output of such models can then be incorporated in graphical process maps and used as a predictive tool to carry out ‘what if’ studies. These may be, for example, on possible changes to the biocatalyst (via directed evolution) or the implementation of innovative process solutions (such as in-situ product removal). In this way, alternative process flow sheets and operating strategies can be evaluated more rapidly. In this paper, the utility of these numerical and graphical techniques using the Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-one by a whole cell biocatalyst expressing cyclohexanone monooxygenase, is illustrated.