Snajdrova Radka, Braun Ingbert, Bach Thorsten, Mereiter Kurt, Mihovilovic Marko D
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, A-1060 Vienna, Austria.
J Org Chem. 2007 Dec 7;72(25):9597-603. doi: 10.1021/jo701704x. Epub 2007 Nov 15.
Bridged cycloketones were synthesized and utilized as substrates to study biooxidations mediated by Baeyer-Villiger monooxygenases (BVMO) of various bacterial origin. The required enzymes were heterologously produced by recombinant overexpression systems based on Escherichia coli to enable facile recycling of the required nicotinamide cofactors during the whole-cell biotransformations. Ketone precursors of various structural demands were chosen to evaluate steric limitations and flexibility of the active site of BVMOs. By desymmetrization of the prochiral substrates, four to six stereogenic centers were generated within a single biooxidation step. The enzyme library investigated in this study allowed access to antipodal lactone products with excellent enantioselectivity in several cases. Together with a distinct substrate acceptance profile, the recently proposed classification into two groups of cycloketone converting BVMOs was supported by the biotransformation results obtained within this study.
合成了桥环酮并将其用作底物，以研究各种细菌来源的拜耳-维利格单加氧酶（BVMO）介导的生物氧化反应。所需的酶通过基于大肠杆菌的重组过表达系统进行异源生产，以便在全细胞生物转化过程中能够轻松回收所需的烟酰胺辅因子。选择了具有各种结构要求的酮前体，以评估BVMO活性位点的空间限制和灵活性。通过前手性底物的去对称化，在单个生物氧化步骤中产生了四到六个立体中心。本研究中研究的酶库在几种情况下能够以优异的对映选择性获得对映体内酯产物。结合独特的底物接受谱，本研究中获得的生物转化结果支持了最近提出的将环酮转化BVMO分为两组的分类方法。
