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

生物催化是酶和微生物在制药、农用化学品和散装化学品生产中的应用。作为更广泛的‘工业生物技术’(IB)领域的一部分，它对基本化学品的生产做出了越来越大的贡献。在某些应用中，生物催化是传统化学合成方法的一种有吸引力的替代方法，因为它提供了对环境友好和高度选择性的过程，这是许多传统催化剂所不具备的。这方面的一个例子是生物催化剂能够产生单一的光学异构体，或其他相同化学产品的‘对映体’，其中不同异构体的性质在生物环境中可能具有非常不同的影响，例如在药物中。化学工业的研究人员一直在寻找新的生物催化剂来取代现有的化学过程，而这些新的酶通常是在微生物中发现的。水合酶是一种生物催化剂，能够将一种形式丰富的石油化学衍生碳氢化合物(称为烯烃)转化为单一异构体形式的合成有价值的醇，这些醇可以作为制药和香料/香料行业的前体。这些新的酶提供了很好的前景，但由于最近才被发现，人们对它们的外观或工作原理知之甚少，如果要设计这些酶来提高活性和工艺适应性，对这些方面的进一步了解是必不可少的。在这个项目中，我们将研究一类新的水合酶类酶，它不仅催化烯烃产生醇，而且能够利用天然生成的醇，在反向反应中将它们转化为非天然的烯烃，如异戊二烯，用于生产包括橡胶在内的聚合物。我们将使用X射线结晶学来确定酶的结构，并使用这些信息来研究酶的工作原理，并为蛋白质工程研究提供信息，这些研究将帮助我们针对不同的应用改变和改进酶。最后，我们将在商业伙伴的协助下，将改进后的酶应用于有用分子的转化，以期为工业过程提供新的选择性和可持续的化学方法。

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.