Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto, Japan.
Department of Biotechnology and Life Science, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Kogane, Tokyo, Japan.
Annu Rev Biomed Eng. 2024 Jul;26(1):357-382. doi: 10.1146/annurev-bioeng-110222-101926. Epub 2024 Jun 20.
Among the various types of enzyme-based biosensors, sensors utilizing enzymes capable of direct electron transfer (DET) are recognized as the most ideal. However, only a limited number of redox enzymes are capable of DET with electrodes, that is, dehydrogenases harboring a subunit or domain that functions specifically to accept electrons from the redox cofactor of the catalytic site and transfer the electrons to the external electron acceptor. Such subunits or domains act as built-in mediators for electron transfer between enzymes and electrodes; consequently, such enzymes enable direct electron transfer to electrodes and are designated as DET-type enzymes. DET-type enzymes fall into several categories, including redox cofactors of catalytic reactions, built-in mediators for DET with electrodes and by their protein hierarchic structures, DET-type oxidoreductases with oligomeric structures harboring electron transfer subunits, and monomeric DET-type oxidoreductases harboring electron transfer domains. In this review, we cover the science of DET-type oxidoreductases and their biomedical applications. First, we introduce the structural biology and current understanding of DET-type enzyme reactions. Next, we describe recent technological developments based on DET-type enzymes for biomedical applications, such as biosensors and biochemical energy harvesting for self-powered medical devices. Finally, after discussing how to further engineer and create DET-type enzymes, we address the future prospects for DET-type enzymes in biomedical engineering.
在各种基于酶的生物传感器中，利用能够直接电子转移 (DET) 的酶的传感器被认为是最理想的。然而，只有少数氧化还原酶能够与电极进行 DET，即具有特定功能以从催化部位的氧化还原辅因子接受电子并将电子转移到外部电子受体的亚基或结构域的脱氢酶。这样的亚基或结构域充当酶和电极之间电子转移的内置介体；因此，这些酶能够实现与电极的直接电子转移，并被指定为 DET 型酶。DET 型酶分为几类，包括催化反应的氧化还原辅因子、与电极进行 DET 的内置介体以及其蛋白质层次结构、具有电子转移亚基的寡聚结构的 DET 型氧化还原酶和具有电子转移结构域的单体 DET 型氧化还原酶。在这篇综述中，我们介绍了 DET 型氧化还原酶的科学及其在生物医学中的应用。首先，我们介绍了 DET 型酶反应的结构生物学和当前的理解。接下来，我们描述了基于 DET 型酶的生物医学应用的最新技术发展，例如生物传感器和用于自供电医疗设备的生化能量收集。最后，在讨论如何进一步设计和创建 DET 型酶之后，我们探讨了 DET 型酶在生物医学工程中的未来前景。
