Department of Biochemistry, Blacksburg, VA, 24061, USA.
Department of Biochemistry, Blacksburg, VA, 24061, USA; Center for Drug Discovery, Virginia Tech, Blacksburg, VA, 24061, USA.
Arch Biochem Biophys. 2021 Mar 15;699:108765. doi: 10.1016/j.abb.2021.108765. Epub 2021 Jan 16.
Flavin-dependent monooxygenases catalyze a wide variety of redox reactions in important biological processes and are responsible for the synthesis of highly complex natural products. Although much has been learned about FMO chemistry in the last ~80 years of research, several aspects of the reactions catalyzed by these enzymes remain unknown. In this review, we summarize recent advancements in the flavin-dependent monooxygenase field including aspects of flavin dynamics, formation and stabilization of reactive species, and the hydroxylation mechanism. Novel catalysis of flavin-dependent N-oxidases involving consecutive oxidations of amines to generate oximes or nitrones is presented and the biological relevance of the products is discussed. In addition, the activity of some FMOs have been shown to be essential for the virulence of several human pathogens. We also discuss the biomedical relevance of FMOs in antibiotic resistance and the efforts to identify inhibitors against some members of this important and growing family enzymes.
黄素依赖单加氧酶在重要的生物过程中催化各种各样的氧化还原反应，并且负责合成高度复杂的天然产物。尽管在过去的 80 年研究中已经了解了 FMO 化学的很多方面，但这些酶催化的反应的几个方面仍然未知。在这篇综述中，我们总结了黄素依赖单加氧酶领域的最新进展，包括黄素动力学、反应性物质的形成和稳定，以及羟化机制。介绍了涉及连续氧化胺生成肟或硝酮的黄素依赖 N-氧化酶的新型催化作用，并讨论了产物的生物学相关性。此外，一些 FMO 的活性已被证明对几种人类病原体的毒力至关重要。我们还讨论了 FMO 在抗生素耐药性中的生物医学相关性，以及识别针对这一重要且不断发展的酶家族成员抑制剂的努力。
