Baeyer-Villiger monooxygenases (BVMOs) are flavoenzymes and belong to the class of oxidoreductases. They catalyse the oxidation of linear, cyclic and aromatic ketones to the corresponding esters or lactones, highly similar to the chemical Baeyer-Villiger oxidation. During the enzymatic oxidation, one atom of molecular oxygen is incorporated into a carbon-carbon bond of a non-activated ketone. Lactones can be produced biocatalytically using Baeyer–Villiger monooxygenases (BVMOs), which are members of a diverse class of flavoprotein monooxygenases. The use of protecting groups and formation of by-products can be avoided in enzymatic processes, simplifying synthesis. BVMOs can show excellent stereoselectivity, and react under relatively mild conditions. Oxidation of ketones by BVMOs, however, is often regio-divergent, generating two lactone products with some substrates. The isomers are produced via migration of the nucleophilic carbon centre, to form the ‘normal’ and ‘abnormal’ isomer, respectively. In Monopoly, we aimed to gain a deeper understanding from a structural/engineering perspective of enzyme catalysis in relation to lactone production by new members of the BVMO family. The overall aim of this Marie Curie CAR fellowship programme is therefore to exploit enzyme kinetics, biocatalysis, structure determination, biophysical analysis and modelling as enabling disciplines to build a tool kit of novel Bayer Villiger monooxygenases as part of a self-consistent Design-Build-Test cycle.
Biomaterials composed of lactone monomers have been used to produce polyurethanes. For example, the synthesis of poly--caprolactones takes place via ring-opening polymerisation (ROP) of a monomeric -caprolactones. Additionally, ketal lactones (oxo-carboxylic ketals) are useful in the production of surfactants, plasticisers, solvents and polymers. Monopoly will lead to the development of new lactone monomers from which new polymers could be generated with improved properties and novel applications, especially in the healthcare arena. Biodegradable poly-lactone materials derived from petrochemical routes are already used widely in industry (e.g. speciality polyurethanes, additives, plasticisers), dentistry (as Resilon composites in splints and fillings) and healthcare (e.g. scaffolds for tissue engineering, drug delivery, bio-adhesives and orthopaedic castings). The sustainable production of monomers for these and related polymers is likely to impact in these areas, especially in the healthcare and dentistry markets where high quality/low volume products are sought.
