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

水合酶/脱水酶的结构、机制和应用：香精、香料和聚合物前体

• 批准号: BB/P005578/1
• 负责人: Gideon Grogan
• 金额: $ 48.97万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP005578%2F1
• 关键词: Structure; Mechanism; Application; Hydratase; Dehydratases

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.

生物催化是将酶和微生物应用于制药、农业化学和大宗化学工业的化学品生产。作为“工业生物技术”（IB）更广泛领域的一部分，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，因为它以许多传统催化剂所不具备的方式提供了环境友好和高度选择性的过程。这方面的一个例子是生物催化剂产生单一光学异构体或其他相同化学产品的“对映异构体”的能力，其中不同异构体的性质在生物学背景下（例如在药物中）可能具有截然不同的效果。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，而这些新的酶通常在微生物中发现。水合酶是生物催化剂，其能够将一种形式的丰富的石油化学衍生的烃（称为烯烃）转化为单一异构体形式的有合成价值的醇，其可以用作药物和调味剂/香料工业的前体。这些新的酶提供了很大的希望，但只是最近才发现的，很少有人知道他们看起来像什么或他们如何工作，和这些方面的进一步知识是必不可少的，如果酶被改造为提高活性和工艺适用性。在这个项目中，我们将研究一类新的水合酶，它不仅催化从烯烃生产醇，而且还能够利用天然存在的醇，并在逆反应中将其转化为非天然烯烃，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射线晶体学确定酶的结构，并使用这些信息来研究酶如何工作，并为蛋白质工程研究提供信息，这将有助于我们改变和改进酶以用于不同的应用。最后，我们将在商业合作伙伴的协助下，将改进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。

项目成果

Structure of the imine reductase from Ajellomyces dermatitidis in three crystal forms.

• DOI: 10.1107/s2053230x23006672
• 发表时间: 2023-09-01
• 期刊: Acta crystallographica. Section F, Structural biology communications

S -Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C -Alkylation

S-腺苷甲硫氨酸辅因子修饰增强小分子 C-烷基化的生物催化能力

• DOI: 10.1002/ange.201908681
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: McKean I

The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides.

• DOI: 10.1002/anie.201804592
• 发表时间: 2018-09-03
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Petchey M;Cuetos A;Rowlinson B;Dannevald S;Frese A;Sutton PW;Lovelock S;Lloyd RC;Fairlamb IJS;Grogan G
• 通讯作者: Grogan G

Mutational Analysis of Linalool Dehydratase Isomerase Suggests That Alcohol and Alkene Transformations Are Catalyzed Using Noncovalent Mechanisms

芳樟醇脱水酶异构酶的突变分析表明酒精和烯烃的转化是通过非共价机制催化的

• DOI: 10.1021/acscatal.0c02958
• 发表时间: 2020
• 期刊: ACS Catalysis
• 影响因子: 12.9
• 作者: Cuetos A