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

在过去，工程蛋白也被证明是非自然转化的有力催化剂。在该项目中，将利用定向进化将环加成反应添加到由血红素酶催化的反应范围内。在合适的蛋白质的帮助下，类卡宾和羰基化合物将生成1，3-偶极。随后的(3+2)-环加成反应导致四氢呋喃和二氢呋喃的生成，我们的目标是不仅以高的非对映选择性，而且以对映体选择性获得这些化合物。这种史无前例的不对称合成草环的方法应该是通过对野生型血红素酶进行顺序位置饱和突变来实现的。

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.