Hengyang Medical School, University of South China, Hengyang 421001, China.
School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China.
Org Lett. 2024 Oct 18;26(41):8872-8877. doi: 10.1021/acs.orglett.4c03314. Epub 2024 Oct 10.
Organoborons have recently received much attention, while a biocatalytic platform for the synthesis of chiral organoborons is limited only to cytochrome . In this study, we exploited the other heme protein, neuroglobin (Ngb), and engineered a quadruple mutant, A15C/H64G/V68F/F28M Ngb, by redesigning the heme active site using the structural information on A15C Ngb and molecular docking studies. The enzyme was shown to be efficient in catalyzing carbene transfer B-H insertion reactions between pyridine/quinoline boranes and benzyl 2-diazopropanoates and their derivatives (29 examples). The designed cavity in the heme distal site favors the binding of large volume substrates such as those containing a quinoline, naphthyl, or biphenyl group. As further determined by the X-ray crystallography of , the chiral products are in the -configuration, with up to 98:2 e.r. Furthermore, both the whole cell and cell lysate containing the enzyme are reactive toward the B-H insertion reactions. This study presents a convenient biocatalytic platform that may be generally applicable for the synthesis of functional chiral organoborons.
有机硼化合物最近受到了广泛关注，而用于手性有机硼化合物合成的生物催化平台仅限于细胞色素。在这项研究中，我们利用另一种血红素蛋白神经球蛋白（Ngb），并通过使用 A15C Ngb 的结构信息和分子对接研究重新设计血红素活性位点，构建了四重突变体 A15C/H64G/V68F/F28M Ngb。结果表明，该酶在手性 carbene 转移 B-H 插入反应中具有很高的催化活性，可催化吡啶/喹啉硼烷与苄基 2-二氮丙酸盐及其衍生物之间的反应（29 个实例）。血红素远端位点的设计腔有利于结合具有较大体积的底物，例如含有喹啉、萘基或联苯基团的底物。进一步通过 X 射线晶体学研究，确定手性产物为 -构型，对映体过量值最高可达 98:2。此外，含有酶的全细胞和细胞裂解物都可对 B-H 插入反应发生反应。本研究提供了一种方便的生物催化平台，可能广泛适用于功能手性有机硼化合物的合成。
