Structure, Mechanism and Application of Hydratase/Dehydratases: Flavours, Fragrances and Polymer Precursors

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Biocatalysis is the application of enzymes and microorganisms to the production of chemicals for the pharmaceutical, agrochemical and bulk chemical industries. As part of the wider field of 'Industrial Biotechnology' (IB) that is making an increasing contribution to the production of essential chemicals. Biocatalysis is an attractive alternative to traditional methods of chemical synthesis in some applications as it provides processes that are environmentally benign and highly selective, in a way that many conventional catalysts are not. One example of this is the ability of biocatalysts to generate single optical isomers, or 'enantiomers' of otherwise identical chemical products, where the properties of different isomers can have vastly different effects in a biological context, such as in a drug. Researchers in the chemical industry are always looking for new biocatalysts to replace established chemical processes, and these new enzymes are often discovered in microbes. Hydratase enzymes are biocatalysts that are capable of turning one form of abundant petrochemically-derived hydrocarbons, known as alkenes, into synthetically valuable alcohols, in single isomer form, which can act as precursors for the pharmaceutical and flavour/fragrance industries. These new enzymes offer great promise, but being only recently discovered, little is known about what they look like or how they work, and further knowledge of these aspects is essential if the enzymes are to be engineered for improved activity and process suitability. In this project, we will study a new class of hydratase enzymes that not only catalyse the production of alcohols from alkenes, but are also able to take naturally occurring alcohols, and, in the reverse reaction, turn them into non-natural alkenes such as isoprene for the production of polymers including rubber. We will determine the structures of the enzymes using X-ray crystallography, and use the information to study how the enzymes work, and to inform protein engineering studies that will help us change and improve the enzymes for different applications. Finally we will, with the assistance of commercial partners, apply the improved enzymes to the transformation of useful molecules, with a view to providing new selective and sustainable methods of chemistry for industrial processes.