Rationalization of a Streptavidin Based Enantioselective Artificial Suzukiase : An Integrative Computational Approach
Tiessler-Sala, Laura (Universitat Autònoma de Barcelona. Departament de Química)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Lledós, Agustí (Universitat Autònoma de Barcelona. Departament de Química)

Date:	2024
Abstract:	An Artificial Metalloenzyme (ArM) built employing the streptavidin-biotin technology has been used for the enantioselective synthesis of binaphthyls by means of asymmetric Suzuki-Miyaura cross-coupling reactions. Despite its success, it remains a challenge to understand how the length of the biotin cofactors or the introduction of mutations to streptavidin leads the preferential synthesis of one atropisomer over the other. In this study, we apply an integrated computational modeling approach, including DFT calculations, protein-ligand dockings and molecular dynamics to rationalize the impact of mutations and length of the biotion cofactor on the enantioselectivities of the biaryl product. The results unravel that the enantiomeric differences found experimentally can be rationalized by the disposition of the first intermediate, coming from the oxidative addition step, and the entrance of the second substrate. The work also showcases the difficulties facing to control the enantioselection when engineering ArM to catalyze enantioselective Suzuki-Miyaura couplings and how the combination of DFT calculations, molecular dockings and MD simulations can be used to rationalize artificial metalloenzymes.
Grants:	Agencia Estatal de Investigación PID2020-116861GB-I00 Ministerio de Ciencia, Innovación y Universidades FPU18/05895
Note:	Altres ajuts: acords transformatius de la UAB
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Artificial metalloenzyme ; Asymmetric SuzukiMiyaura coupling ; Biaryl ; Integrative computational approach ; Molecular modeling
Published in:	Chemistry (Weinheim), Vol. 30, Núm. 39 (July 2024) , art. e202401165, ISSN 1521-3765

DOI: 10.1002/chem.202401165

14 p, 2.2 MB

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