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New frontiers in flavin-dependent monooxygenases
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2021-01-16 , DOI: 10.1016/j.abb.2021.108765
Renata A.G. Reis , Hao Li , Maxim Johnson , Pablo Sobrado

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 ∼60 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.



中文翻译:

黄素依赖性单加氧酶的新领域

黄素依赖性单加氧酶在重要的生物过程中催化多种氧化还原反应,并负责合成高度复杂的天然产物。尽管在过去约60年的研究中已经学到了很多有关FMO化学的知识,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性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基化机理。黄素依赖性氮的新型催化提出了涉及胺连续氧化以生成肟或硝酮的β-氧化酶,并讨论了产物的生物学相关性。此外,一些FMO的活性已显示对于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,以及确定针对这种重要且正在增长的家族酶某些成员的抑制剂的工作。

更新日期:2021-01-18
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