The history of the development of glucose sensors goes hand-in-hand with the history of the discovery and the engineering of glucose-sensing enzymes. Glucose oxidase (GOx) has been used for glucose sensing since the development of the first electrochemical glucose sensor. The principle utilizing oxygen as the electron acceptor is designated as the first-generation electrochemical enzyme sensors. With increasing demand for hand-held and cost-effective devices for the "self-monitoring of blood glucose (SMBG)", second-generation electrochemical sensor strips employing electron mediators have become the most popular platform. To overcome the inherent drawback of GOx, namely, the use of oxygen as the electron acceptor, various glucose dehydrogenases (GDHs) have been utilized in second-generation principle-based sensors. Among the various enzymes employed in glucose sensors, GDHs harboring FAD as the redox cofactor, FADGDHs, especially those derived from fungi, fFADGDHs, are currently the most popular enzymes in the sensor strips of second-generation SMBG sensors. In addition, the third-generation principle, employing direct electron transfer (DET), is considered the most elegant approach and is ideal for use in electrochemical enzyme sensors. However, glucose oxidoreductases capable of DET are limited. One of the most prominent GDHs capable of DET is a bacteria-derived FADGDH complex (bFADGDH). bFADGDH has three distinct subunits; the FAD harboring the catalytic subunit, the small subunit, and the electron-transfer subunit, which makes bFADGDH capable of DET. In this review, we focused on the two representative glucose sensing enzymes, fFADGDHs and bFADGDHs, by presenting their discovery, sources, and protein and enzyme properties, and the current engineering strategies to improve their potential in sensor applications.

中文翻译：

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FAD依赖性葡萄糖脱氢酶-代表性葡萄糖传感酶的发现和工程设计。

葡萄糖传感器的发展历史与葡萄糖传感酶的发现和工程化历史息息相关。自从第一个电化学葡萄糖传感器问世以来，葡萄糖氧化酶（GOx）就已经用于葡萄糖传感。利用氧作为电子受体的原理被称为第一代电化学酶传感器。随着对用于“血糖自我监测（SMBG）”的手持式且具有成本效益的设备的需求不断增长，采用电子介体的第二代电化学传感器条已成为最受欢迎的平台。为了克服GOx的固有缺点，即使用氧气作为电子受体，在第二代基于原理的传感器中已使用了各种葡萄糖脱氢酶（GDH）。在葡萄糖传感器中使用的各种酶中，以FAD为氧化还原辅助因子的GDH，FADGDH（尤其是衍生自真菌的fDGDGDH）目前是第二代SMBG传感器传感器条中最受欢迎的酶。此外，采用直接电子转移（DET）的第三代原理被认为是最优雅的方法，非常适合用于电化学酶传感器。然而，能够DET的葡萄糖氧化还原酶是有限的。能够DET的最杰出的GDH之一是细菌衍生的FADGDH复合物（bFADGDH）。bFADGDH具有三个不同的亚基；FAD包含催化亚基，小亚基和电子转移亚基，这使bFADGDH具有DET能力。在这篇评论中，我们重点介绍了两种代表性的葡萄糖传感酶，fFADGDHs和bFADGDHs，