Expanding the substrate and biological scopes of lytic polysaccharide monooxygenases

扩大溶解多糖单加氧酶的底物和生物学范围

• 批准号: BB/V004069/1
• 负责人: Paul Walton
• 金额: $ 70.71万
• 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: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV004069%2F1
• 关键词: Expanding; substrate; biological; scopes; lytic

Enzymes are nature's catalysts; they speed up chemical reactions which otherwise would take too long to be useful. Such is the power of enzymes to do this, that they have been utilised in very many applications. For instance, modern washing powders contain enzymes that breakdown the stains on clothes, but do this at temperatures which mean that washing can be done at a low temperature, saving energy. Another example is where enzymes are used in pregnancy testing kits to deliver highly accurate and rapid results. Despite the great advances in enzyme technology however, there is a gap in our understanding. This gap comes when an enzyme has to react with a solid substrate, say plastic or biomass. Here the substrate is so large that it cannot be 'wrapped-up' by the enzyme (as normal enzymes do when the substrate enters into the so-called active site of the enzyme). This inability to wrap-up a substrate detracts from some of the power of enzymes to speed up reactions by distorting and bending the shape of substrates such that they become reactive. This gap is serious, as there are many solid substrates which humankind would like to breakdown using enzymes. These include waste plant matter (that could be turned into fuel for instance) or waste plastics (which currently contaminate our oceans). This project is focussed on a recently discovered class of enzymes called lytic polysaccharide monooxygenases (LPMOs), which have been shown to breakdown cellulose (plant matter) which is an highly unreactive solid substrate. The power of LPMOs to catalyse this reaction is extraordinary, and is now posing new questions on how biology uses enzymes to breakdown solid matter. We seek to investigate the range of substrates that can be broken down by completely new classes of LPMOs that we have found using a technique called genome mining. We will isolate and study these enzymes in great detail, trying to understanding their chemical features and-most importantly-see if we can turn their properties to destroy solid matter towards societal good, in this case whether we can use these new LPMOs in insect control where they can be employed to breakdown the cuticles of mosquitoes.

酶是自然界的催化剂;它们加速化学反应，否则化学反应需要太长时间才能发挥作用。这就是酶的力量，它们已经被用于许多应用中。例如，现代洗衣粉含有分解衣服上污渍的酶，但在温度下进行，这意味着洗涤可以在低温下进行，从而节省能源。另一个例子是在妊娠测试试剂盒中使用酶，以提供高度准确和快速的结果。尽管酶技术取得了巨大的进步，但我们的理解仍存在差距。当酶必须与固体基质（如塑料或生物质）反应时，就会出现这种差距。在这里，底物是如此之大，以至于它不能被酶“包裹”（就像正常的酶在底物进入酶的所谓活性位点时所做的那样）。这种不能包裹底物的能力削弱了酶通过扭曲和弯曲底物的形状来加速反应的能力，使得它们变得具有反应性。这个差距是严重的，因为有许多固体基质，人类希望使用酶分解。这些包括废弃植物物质（例如，可以转化为燃料）或废塑料（目前污染我们的海洋）。该项目的重点是最近发现的一类酶，称为溶解性多糖单加氧酶（LPMO），已被证明可以分解纤维素（植物物质），这是一种高度不反应的固体基质。LPMO催化这一反应的能力是非凡的，现在正在提出生物学如何使用酶分解固体物质的新问题。我们试图调查的范围内的基板，可以打破了全新的类LPMO，我们发现使用一种技术称为基因组挖掘。我们将分离并详细研究这些酶，试图了解它们的化学特征，最重要的是，看看我们是否可以将它们的特性转化为社会利益，在这种情况下，我们是否可以将这些新的LPMO用于昆虫控制，它们可以用来分解蚊子的幼虫。

项目成果

The histidine-brace active site of a copper monooxygenase is redox active and forms part of an in-built enzyme repair mechanism

铜单加氧酶的组氨酸支架活性位点具有氧化还原活性，是内置酶修复机制的一部分

• DOI: 10.21203/rs.3.rs-1350705/v1
• 发表时间: 2022
• 作者: Zhao J

Structural perturbations of substrate binding and oxidation state changes in a lytic polysaccharide monooxygenase.

• DOI: 10.1007/s00775-022-01966-z
• 发表时间: 2022-12
• 期刊: JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
• 影响因子: 3
• 作者: Walton, Paul H.;Davies, Gideon J.
• 通讯作者: Davies, Gideon J.

Mapping the Initial Stages of a Protective Pathway that Enhances Catalytic Turnover by a Lytic Polysaccharide Monooxygenase.

• DOI: 10.1021/jacs.3c06607
• 发表时间: 2023-09-20
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Zhao, Jingming;Zhuo, Ying;Diaz, Daniel E.;Shanmugam, Muralidharan;Telfer, Abbey J.;Lindley, Peter J.;Kracher, Daniel;Hayashi, Takahiro;Seibt, Lisa S.;Hardy, Florence J.;Manners, Oliver;Hedison, Tobias M.;Hollywood, Katherine A.;Spiess, Reynard;Cain, Kathleen M.;Diaz-Moreno, Sofia;Scrutton, Nigel S.;Tovborg, Morten;Walton, Paul H.;Heyes, Derren J.;Green, Anthony P.
• 通讯作者: Green, Anthony P.