Increasing the enantioselectivity of cyclopentanone monooxygenase (CPMO): profile of new CPMO mutants |
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| Affiliation: | 1. Equipe “Biomolécules Fluorées”, Chimie Organique Bioorganique Réactivité et Analyses (COBRA), Institut de Recherche en Chimie Organique Fine de Rouen (IRCOF), UMR CNRS 6014, Université et Institut National des Sciences Appliquées (INSA) de Rouen, F-76821 Mont Saint Aignan Cedex, France;2. Equipe “Synthèse de Molécules d’Intérêt Thérapeutique (SMITH)”, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), UMR CNRS-UCBL-INSA Lyon 5246, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Bâtiment Curien, 43 bd du 11 Novembre 1918, F-69622 Villeurbanne, France;3. Malaria Research Unit (MRU), Faculté de Médecine, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon Cedex, France;1. Guizhou Engineering Center for Innovative Traditional Chinese Medicine and Ethnic Medicine, College of Pharmacy, Guizhou University, Guiyang 550025, China;2. Key Laboratory for Asymmetric Synthesis & Chirotechnology of Sichuan Province, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, China;1. State Key Laboratory of Environmental and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;1. Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, PR China;2. Beijing National Laboratory for Molecular Sciences (BNLMS), Peking University, Beijing 100871, PR China |
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| Abstract: | A series of cyclohexanones substituted at the 4-position with a selection of hydrophobic and hydrophilic groups were used as substrates in the evaluation of six new cyclopentanone monooxygenase (CPMO) mutants. These mutants were obtained through evolutionary modifications in two specific regions of the CPMO’s putative active site. Several mutant enzymes with improved enantioselectivity were identified. Analysis of the results, in terms of a diamond model, illustrates how a family of cyclohexanone substrates may be used to explore putative active sites of Baeyer–Villiger monooxygenases (BVMOs) and to design productive mutations for specific substrates. |
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