Artificial metalloenzymes engineered from non-heme enzymes

由非血红素酶改造而成的人工金属酶

• 批准号: 2424538
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2424538
• 关键词: Artificial; metalloenzymes; engineered; non; heme

Non-heme enzymes are known to catalyse a whole range of versatile reactions given rise to numerous complex natural products. They are most commonly known for oxidative reactions, in which active sites containing 2-his-1-carboxylate triad are often found. This same motif is also observed in other classes of enzymes including the halogenases. Halogenases such as SyrB2, HctB and WeIO5 are -ketoglutarase dependent enzymes, in which an iron-oxo intermediate is formed but subtle positioning of the amino acid residues displace the activity from oxidation to halogenation. SyrB2 shows promiscuous behaviour and can also catalyse azidation and nitration, albeit with low yields. One limitation of this enzyme for use in organic synthesis is the requirement for the substrate to be delivered by a ACP i.e. it can only be used to functionalise fatty acids. WeIO5 has been found to accept free substrates and thus provides a more promising template for organic synthesis. In recent work it has been a variant of WeIO5, WeIO5* has been shown to accept substrates beyond its natural indole substrates and to also accept NaBr alongside NaCl.

已知非血红素酶催化产生许多复杂的天然产物的一系列通用反应。它们最常用于氧化反应，其中经常发现含有2-His-1-羧酸三联体的活性位点。在包括卤酶在内的其他类型的酶中也观察到了相同的基序。卤代酶如SyrB 2、HctB和WeIO 5是β-酮戊二酸酶依赖性酶，其中形成铁-氧代中间体，但氨基酸残基的微妙定位将活性从氧化置换为卤化。SyrB 2表现出混杂的行为，也可以催化叠氮化和硝化，尽管产率较低。这种酶用于有机合成的一个限制是需要由ACP递送底物，即它只能用于官能化脂肪酸。已发现WeIO 5接受自由底物，因此为有机合成提供了更有前途的模板。在最近的工作中，它已经是WeIO 5的变体，WeIO 5 * 已经显示出接受其天然吲哚底物以外的底物，并且还接受NaBr以及NaCl。