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Biocatalytic Baeyer-Villiger Reactions: Uncovering the Source of Regioselectivity at Each Evolutionary Stage of a Mutant with Scrutiny of Fleeting Chiral Intermediates

文献类型： 外文期刊

作者： Dong, Yijie 1 ; Li, Tang 3 ; Zhang, Shiqing 4 ; Sanchis, Joaquin 6 ; Yin, Heng 3 ; Ren, Jie 1 ; Sheng, Xiang 4 ; Li, Guangyue 1 ; Reetz, Manfred T. 4 ;

作者机构： 1.Chinese Acad Agr Sci, State Key Lab Biol Plant Dis & Insect Pests, Key Lab Control Biol Hazard Factors Plant Origin, Inst Plant Protect, Beijing 100193, Peoples R China

2.Guangdong Acad Sci, Key Lab Agr Microbi & Precis Applicat,Guangdong M, Minist Agr & Rural Affairs,State Key Lab Appl Mic, Guangdong Prov Key Lab Microbial Culture Collect, Guangzhou 510070, Peoples R China

3.Chinese Acad Sci, Dalian Inst Chem Phys, Liaoning Prov Key Lab Carbohydrates, Dalian 116023, Liaoning, Peoples R China

4.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin 300308, Peoples R China

5.Natl Ctr Technol Innovat Synthet Biol, Tianjin 300308, Peoples R China

6.Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

7.Max Planck Inst Kohlenforsch, D-45470 Mulheim, Germany

关键词： biocatalytic Baeyer-Villiger reaction; regioselectivity; Criegee intermediate; deconvolution; quantum chemical calculations

期刊名称：ACS CATALYSIS （ 影响因子：13.7； 五年影响因子：14.413 ）

ISSN： 2155-5435

年卷期： 2022 年 12 卷 6 期

页码：

收录情况： SCI

摘要： In this study, we report the discovery of unexpected mechanistic intricacies of Baeyer-Villiger monooxygenases (BVMOs) and provide insights that promise to help in extending their applications in synthetic organic chemistry and biotechnology. The basic mechanism of BVMOs as catalysts in the oxidation of unsymmetrical ketones R-1- (C=O)-R-2 is well known, which involves the intermediacy of short-lived Criegee intermediates. The tendency of R-1 or R-2 to migrate preferentially in the breakdown of the Criegee intermediate follows the traditional requirement of an antiperiplanar conformation with maximum stabilization of the incipient positive charge. The challenge of inverting the regioselectivity of group migration with the formation of abnormal products was recently met by the semi-rational directed evolution of TmCHMO with the generation of a quadruple mutant. Although a reasonable model explaining the mutational effect was suggested, the theoretical analysis did not include the calculation of both enantiomeric forms of the fleeting chiral Criegee intermediate in transition states and focused only on the wild-type enzyme and the quadruple mutant. The present investigation utilizes complete mutational deconvolution with the experimental construction of a fitness-pathway landscape comprising 4! = 24 upward climbs. We were confronted by the discovery that the absolute configuration of the Criegee intermediate switches from (R) to (S), depending upon the stage of the evolutionary process. On the basis of X-ray structural data, the physical basis of this phenomenon was illuminated by quantum chemical analyses performed on the enzymes at all evolutionary steps of a selected pathway. The hitherto unexplored role of fleeting chiral intermediates in the mechanism of other enzyme types deserves increased attention.

  • 相关文献

[1]Biocatalytic Baeyer-Villiger Reactions: Uncovering the Source of Regioselectivity at Each Evolutionary Stage of a Mutant with Scrutiny of Fleeting Chiral Intermediates. Dong, Yijie,Ren, Jie,Li, Guangyue,Dong, Yijie,Li, Tang,Yin, Heng,Zhang, Shiqing,Sheng, Xiang,Reetz, Manfred T.,Zhang, Shiqing,Sanchis, Joaquin. 2022

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