Controllable stereoinversion in DNA-catalyzed olefin cyclopropanation via cofactor modification |
| |
Authors: | Jingya Hao Wenhui Miao Shengmei Lu Yu Cheng Guoqing Jia Can Li |
| |
Institution: | State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, Dalian 116023 China.; University of Chinese Academy of Sciences, Beijing 101408 China |
| |
Abstract: | The assembly of DNA with metal-complex cofactors can form promising biocatalysts for asymmetric reactions, although catalytic performance is typically limited by low enantioselectivities and stereo-control remains a challenge. Here, we engineer G-quadruplex-based DNA biocatalysts for an asymmetric cyclopropanation reaction, achieving enantiomeric excess (eetrans) values of up to +91% with controllable stereoinversion, where the enantioselectivity switches to −72% eetrans through modification of the Fe-porphyrin cofactor. Complementary circular dichroism, nuclear magnetic resonance, and fluorescence titration experiments show that the porphyrin ligand of the cofactor participates in the regulation of the catalytic enantioselectivity via a synergetic effect with DNA residues at the active site. These findings underline the important role of cofactor modification in DNA catalysis and thus pave the way for the rational engineering of DNA-based biocatalysts.Cofactor modification in a DNA-catalyzed olefin cyclopropanation reaction enables controllable stereoinversion and achieves enantioselectivities of up to +91% and −72% eetrans. |
| |
Keywords: | |
|
|