通过含有贵金属代替铁的人工血红蛋白进行非生物催化
Hanna M Key1,2, Paweł Dydio1,2, Douglas S Clark3,4
1Department of Chemistry, University of California, Berkeley, California 94720, USA.
Nature
|June 15, 2016
概括
研究人员通过用像这样的贵金属替代蛋白质中的铁,制造出新的人工酶. 这些工程金属酶催化新的化学反应,包括C-H键功能化和选择性循环化,扩大了生物催化的可能性.
科学领域:
- 生物化学和生物工程
- 催化和酶工程
- 合成化学
背景情况:
- 金属酶利用过渡金属中心进行催化,其反应能力可以通过分子进化和蛋白质工程调整.
- 现有的生物转化策略包括修改本地金属酶或创建具有贵金属复合物的人工金属蛋白.
- 这些方法面临着诸如固有的金属反应性约束或改变的基质结合相互作用的局限性.
研究的目的:
- 通过将金属酶中的原生金属替换为非生物金属,开发一种创造人工酶的新策略.
- 设计能够在原生基质结合部位内催化生物转化的人造酶.
- 探索定向进化的潜力,以优化这些人工酶的催化活性和选择性.
主要方法:
- 在Fe-porphyrin IX (Fe-PIX) 蛋白中以非生物贵金属正式取代铁,特别是产生含有的肌球蛋白 (Ir(Me) 变体.
- 通过碳插入和碳添加反应对工程化Ir(Me) - 肌球蛋白进行催化评估.
- 应用导向进化到Ir(Me) - 肌球蛋白以产生具有增强的C-H插入和循环化反应的突变物.
主要成果:
- 成功制备了含有非生物金属氨酸的人造血蛋白.
- 通过将碳素插入各种基质,证明Ir(Me) - 肌球蛋白催化C-H键功能化形成C-C键.
- 在C-H插入和循环化反应中产生具有高反选择性和异选择性的Ir(Me) - 肌球蛋白的定向进化突变.
结论:
- 用非生物金属替代金属酶中的原生金属的策略为新型催化酶提供了强大的途径.
- 改造的Ir(Me) - 肌球蛋白作为一种多功能的人造酶,能够高选择性催化生物碳转移反应.
- 这种方法可以通过结合各种蛋白质支架和非自然金属辅因子来创建多种人工酶,从而实现广泛的生物转化.
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