Conversion of a Flavoprotein Reductase to a Desaturase by Manipulation of the Flavin Redox Potential
Conversion of a Flavoprotein Reductase to a Desaturase by Manipulation of the Flavin Redox Potential
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通过操纵黄素氧化还原电位将黄素蛋白还原酶转化为去饱和酶
DOI：
10.1021/ja990908t
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发表时间：
1999
影响因子：
15
通讯作者：
V. Massey
中科院分区：
文献类型：
--
作者：
Y. V. Murthy;Y. Meah;V. Massey
最近，在探索酶以高选择性实现化学转化的能力方面出现了一股热潮。1重组DNA技术和定点诱变的出现以及有机溶剂等非常规反应介质的使用导致了酶的有效操作和半合成酶的设计。2.去除黄素辅基以获得脱辅基蛋白，然后用化学修饰的黄素重构脱辅基蛋白相对容易，这一事实为黄素蛋白提供了操纵其催化活性的手段。3在本通讯中，我们报告了通过这种策略成功地将黄素酶NADPH依赖性还原酶转化为氧依赖性去饱和酶。R，β-不饱和酮或烯酮官能团在有机化学中享有独特的地位，因为它参与了多种反应，如1，2-加成或1，4-共轭加成，烷基化或Diels-Alder反应。它也是许多天然产品的一部分。4然而，简单羰基化合物在温和条件下直接选择性催化氧化成其相应的R，β-不饱和衍生物（烯酮）是使用常规合成方法最难实现的反应之一。
Recently there has been a surge of activity in exploring the ability of enzymes to effect chemical transformations with high selectivity. 1 The advent of recombinant DNA technology and sitedirected mutagenesis and the use of nonconventional reaction media like organic solvents has resulted in the effective manipulation of enzymes and in the design of semisynthetic enzymes. 2 The fact that it is relatively easy to remove the flavin prosthetic group to obtain apoprotein and then reconstitute the apoprotein with chemically modified flavins provides flavoproteins with a means of manipulating their catalytic activity. 3 In the present communication we report successful conversion of a flavoenzyme NADPH-dependent reductase to an oxygen-dependent desaturase by this strategy.The R, β-unsaturated ketone or enone functionality enjoys a unique position in organic chemistry as it is involved in a diverse array of reactions such as 1, 2-additions or 1, 4-conjugate additions, alkylations, or Diels-Alder reactions. It is also a part of numerous natural products. 4 However, the selective catalytic oxidation of simple carbonyl compounds directly to their corresponding R, β-unsaturated derivatives (enones) under mild conditions is one of the most difficult reactions to achieve using conventional synthetic methods.