Engineered Heme Enzymes for the Biocatalytic Cycloaddition of Carbonyl Ylides and C–C Multiple Bonds

用于羰基叶立德和 CâC 多重键生物催化环加成的工程血红素酶

• 批准号: 412008750
• 负责人: Dr. Susanne Bähr
• 金额: --
• 依托单位: Division of Chemistry and Chemical Engineering
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/412008750?language=en
• 关键词: Engineered; Heme; Enzymes; Biocatalytic; Cycloaddition

Engineered proteins turned out as potent catalysts also for non-natural transformations in the past. Within this project, directed evolution will be utilized to add cycloadditions to the scope of reactions that are catalyzed by heme enzymes. With the aid of a suitable protein, a 1,3-dipole will be generated from a carbenoid and a carbonyl compound. Subsequent (3+2)-cycloaddition results in the formation of tetra- and dihydrofurans, which we aim to obtain not only with high diastereoselectivity, but also enantioselectively. This unprecedented method for the asymmetric synthesis of oxacycles should be achieved through sequential site-saturation mutagenesis of the wild-type heme enzyme.

在过去，工程蛋白质也被证明是非自然转化的有效催化剂。在这个项目中，定向进化将被用来增加环加成反应的范围，由血红素酶催化。借助于合适的蛋白质，将由类卡宾和羰基化合物产生1，3-偶极。随后的（3+2）-环加成的结果在形成四-和二氢呋喃，我们的目标是获得不仅具有高的非对映选择性，但也对映选择性。这种前所未有的不对称合成氧杂环化合物的方法应该通过对野生型血红素酶的连续位点饱和诱变来实现。