Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
Curr Opin Chem Biol. 2024 Jun;80:102464. doi: 10.1016/j.cbpa.2024.102464. Epub 2024 May 12.
Flavoenzymes catalyze numerous redox reactions including the transfer of an O-derived oxygen atom to organic substrates, while the other one is reduced to water. Investigation of some of these monooxygenases led to a detailed understanding of their catalytic cycle, which involves the flavin-C-(hydro)peroxide as hallmark oxygenating species, and newly discovered flavoprotein monooxygenases were generally assumed to operate similarly. However, discoveries in recent years revealed a broader mechanistic versatility, including enzymes that utilize flavin-N oxygen adducts for catalysis in the form of the flavin-N-(hydro)peroxide and the flavin-N-oxide species. In this review, I will highlight recent developments in that area, including noncanonical flavoenzymes from natural product biosynthesis and sulfur metabolism that provide first insights into the chemical properties of these species. Remarkably, some enzymes may even combine the flavin-N-peroxide and the flavin-N-oxide species for consecutive oxygen-transfers to the same substrate and thereby in essence operate as dioxygenases.
黄素酶催化许多氧化还原反应，包括将一个 O 衍生的氧原子转移到有机底物上，而另一个则被还原为水。对其中一些单加氧酶的研究导致了对其催化循环的详细了解，该循环涉及黄素-C-（过）氧化物作为标志性的含氧物种，而新发现的黄素蛋白单加氧酶通常被认为具有类似的作用方式。然而，近年来的发现揭示了更广泛的机制多样性，包括利用黄素-N 氧加合物作为黄素-N-（过）氧化物和黄素-N-氧化物形式进行催化的酶。在这篇综述中，我将重点介绍该领域的最新进展，包括天然产物生物合成和硫代谢中的非典型黄素酶，这些酶为这些物种的化学性质提供了初步的见解。值得注意的是，一些酶甚至可以将黄素-N-过氧化物和黄素-N-氧化物结合起来，对同一底物进行连续的氧转移，从而实质上作为双加氧酶发挥作用。
