Prof. Dr. Thomas R. Ward Department of Chemistry Profiles & Affiliations OverviewResearch Publications Projects & Collaborations Projects & Collaborations OverviewResearch Publications Projects & Collaborations Profiles & Affiliations Projects & Collaborations 37 foundShow per page10 10 20 50 Continuous Evolution of Artificial Catalysts into Life-Sustaining Enzymes Research Project | 1 Project MembersImported from Grants Tool 4701415 Biocatalytic Production of 2-Hydroxy carboxylic Acids Using Oxidative Enzymes Research Project | 2 Project MembersNo Description available Design and Directed Evolution of Artificial Metalloenzymes with Shielded Active Sites Research Project | 1 Project MembersNo Description available MetRaZymes - Metal-containing Radical Enzymes Research Project | 1 Project MembersNo Description available Development of an artificial ribozyme: towards new-to-nature metabolism Research Project | 2 Project MembersDevelopment of an artificial ribozyme: towards new-to-nature metabolis. NCCR Catalysis - Sustainable Chemical Processes Through Catalysis Research Project | 1 Project MembersSustainable chemical processes through catalyst design. ICEEL 2020 Research Project | 2 Project MembersNo Description available ICMSE 2021 Research Project | 2 Project MembersNo Description available PhotoArM - Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis Research Project | 2 Project MembersPhotoredox catalysis has recently been established as a powerful method of achieving unconventional chemical reactivity via open-shell reaction intermediates. In combination with the high reactivity of transition metal catalysis, metallaphotoredox catalysis has allowed the coupling of non-traditional partners under mild conditions. 1 However, achieving these reactions selectively remains an ongoing challenge. 2 Concomitantly, efforts to combine the control offered by enzymes with the expanded reaction repertoire of abiotic cofactors have yielded many examples of artificial metalloenzymes capable of carrying out highly selective unnatural reactions. 3 Unifying the unconventional reactivity of metallaphotoredox catalysis with the unparalleled levels of control offered by enzymes would give a new class of artificial metallaphotoredoxenzymes (PhotoArMs) Herein we investigate the development of novel PhotoArMs based on the biotin-streptavidin technology powered by an external photocatalyst to carry out enantioselective coupling reactions. 1) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw, R. W. Evans and D. W. C. MacMillan, Nat. Rev. Chem. 2017 , 1 , 0052 2) M. Silvi and P. Melchiorre, Nature 2018 , 554 , 41 3) F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M.M. Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J.C. Lewis and T.R. Ward, Chem. Rev. 2018 , 118 , 142 Directed Evolution of Artificial Metalloproteins and Metalloenzymes Research Project | 1 Project MembersArtificial metalloenzymes have emerged as a prolific field of research in the past decade. Such hybrid biosystems result from the incorporation of a metallocofactor within a protein scaffold to endow the macromolecule with novel catalytic properties. Thanks to the progress achieved in recombinant protein expression and evolution, artificial metalloproteins offer an attractive means to complement or substitute natural enzymes. Building on the group's expertize in the design and optimization of artificial metalloenzymes, this proposal sets out develop artificial monooxygenases based on the biotin-streptavidin technology. This work complements our work on C-H activation relying on Rh-based artificial metalloenzymes (Hyster et. al., Science 2012, 338, 500). The field of bioinorganic chemistry has developed a handful of nitrogen-based small coordination compounds containing earth-abundant metals that, in combination with hydrogen peroxide, have been used for the oxidation of hydrocarbons. Building on this, we will prepare a series of iron- and manganese complexes bearing biotinylated tetradentate aminopyridine ligands. Their activity will be screened in the presence of streptavidin. A chemo-genetic optimization strategy will be initially applied to improve the performance of the artificial monooxygenases. For this purpose, a series of model alkanes and alkyl ethers with increasing C-H bond dissociation energies will be screened using a 96-well plate format. Next, it is proposed to implement an E. coli surface display of streptavidin to significantly increase the throughput of the directed evolution effort. Here, we will rely on a fluorescence-activated droplet sorting high-throughput screen using coumarin methyl-ether as pro-fluorescent substrate. With the aim of exploiting artificial monooxygenases for the late-stage functionalization of complex molecules, we will subsequently evolve the regioselectivity of the most promising biohybrids. We anticipate that such systems may offer attractive alternatives to both natural enzymes and small molecule catalysts for the (late-stage) functionalization of inert C-H bonds. 1234 1...4 OverviewResearch Publications Projects & Collaborations
Projects & Collaborations 37 foundShow per page10 10 20 50 Continuous Evolution of Artificial Catalysts into Life-Sustaining Enzymes Research Project | 1 Project MembersImported from Grants Tool 4701415 Biocatalytic Production of 2-Hydroxy carboxylic Acids Using Oxidative Enzymes Research Project | 2 Project MembersNo Description available Design and Directed Evolution of Artificial Metalloenzymes with Shielded Active Sites Research Project | 1 Project MembersNo Description available MetRaZymes - Metal-containing Radical Enzymes Research Project | 1 Project MembersNo Description available Development of an artificial ribozyme: towards new-to-nature metabolism Research Project | 2 Project MembersDevelopment of an artificial ribozyme: towards new-to-nature metabolis. NCCR Catalysis - Sustainable Chemical Processes Through Catalysis Research Project | 1 Project MembersSustainable chemical processes through catalyst design. ICEEL 2020 Research Project | 2 Project MembersNo Description available ICMSE 2021 Research Project | 2 Project MembersNo Description available PhotoArM - Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis Research Project | 2 Project MembersPhotoredox catalysis has recently been established as a powerful method of achieving unconventional chemical reactivity via open-shell reaction intermediates. In combination with the high reactivity of transition metal catalysis, metallaphotoredox catalysis has allowed the coupling of non-traditional partners under mild conditions. 1 However, achieving these reactions selectively remains an ongoing challenge. 2 Concomitantly, efforts to combine the control offered by enzymes with the expanded reaction repertoire of abiotic cofactors have yielded many examples of artificial metalloenzymes capable of carrying out highly selective unnatural reactions. 3 Unifying the unconventional reactivity of metallaphotoredox catalysis with the unparalleled levels of control offered by enzymes would give a new class of artificial metallaphotoredoxenzymes (PhotoArMs) Herein we investigate the development of novel PhotoArMs based on the biotin-streptavidin technology powered by an external photocatalyst to carry out enantioselective coupling reactions. 1) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw, R. W. Evans and D. W. C. MacMillan, Nat. Rev. Chem. 2017 , 1 , 0052 2) M. Silvi and P. Melchiorre, Nature 2018 , 554 , 41 3) F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M.M. Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J.C. Lewis and T.R. Ward, Chem. Rev. 2018 , 118 , 142 Directed Evolution of Artificial Metalloproteins and Metalloenzymes Research Project | 1 Project MembersArtificial metalloenzymes have emerged as a prolific field of research in the past decade. Such hybrid biosystems result from the incorporation of a metallocofactor within a protein scaffold to endow the macromolecule with novel catalytic properties. Thanks to the progress achieved in recombinant protein expression and evolution, artificial metalloproteins offer an attractive means to complement or substitute natural enzymes. Building on the group's expertize in the design and optimization of artificial metalloenzymes, this proposal sets out develop artificial monooxygenases based on the biotin-streptavidin technology. This work complements our work on C-H activation relying on Rh-based artificial metalloenzymes (Hyster et. al., Science 2012, 338, 500). The field of bioinorganic chemistry has developed a handful of nitrogen-based small coordination compounds containing earth-abundant metals that, in combination with hydrogen peroxide, have been used for the oxidation of hydrocarbons. Building on this, we will prepare a series of iron- and manganese complexes bearing biotinylated tetradentate aminopyridine ligands. Their activity will be screened in the presence of streptavidin. A chemo-genetic optimization strategy will be initially applied to improve the performance of the artificial monooxygenases. For this purpose, a series of model alkanes and alkyl ethers with increasing C-H bond dissociation energies will be screened using a 96-well plate format. Next, it is proposed to implement an E. coli surface display of streptavidin to significantly increase the throughput of the directed evolution effort. Here, we will rely on a fluorescence-activated droplet sorting high-throughput screen using coumarin methyl-ether as pro-fluorescent substrate. With the aim of exploiting artificial monooxygenases for the late-stage functionalization of complex molecules, we will subsequently evolve the regioselectivity of the most promising biohybrids. We anticipate that such systems may offer attractive alternatives to both natural enzymes and small molecule catalysts for the (late-stage) functionalization of inert C-H bonds. 1234 1...4
Continuous Evolution of Artificial Catalysts into Life-Sustaining Enzymes Research Project | 1 Project MembersImported from Grants Tool 4701415
Biocatalytic Production of 2-Hydroxy carboxylic Acids Using Oxidative Enzymes Research Project | 2 Project MembersNo Description available
Design and Directed Evolution of Artificial Metalloenzymes with Shielded Active Sites Research Project | 1 Project MembersNo Description available
MetRaZymes - Metal-containing Radical Enzymes Research Project | 1 Project MembersNo Description available
Development of an artificial ribozyme: towards new-to-nature metabolism Research Project | 2 Project MembersDevelopment of an artificial ribozyme: towards new-to-nature metabolis.
NCCR Catalysis - Sustainable Chemical Processes Through Catalysis Research Project | 1 Project MembersSustainable chemical processes through catalyst design.
PhotoArM - Directed Evolution of Photoredox Powered Artificial Metalloenzymes for Stereodivergent Catalysis Research Project | 2 Project MembersPhotoredox catalysis has recently been established as a powerful method of achieving unconventional chemical reactivity via open-shell reaction intermediates. In combination with the high reactivity of transition metal catalysis, metallaphotoredox catalysis has allowed the coupling of non-traditional partners under mild conditions. 1 However, achieving these reactions selectively remains an ongoing challenge. 2 Concomitantly, efforts to combine the control offered by enzymes with the expanded reaction repertoire of abiotic cofactors have yielded many examples of artificial metalloenzymes capable of carrying out highly selective unnatural reactions. 3 Unifying the unconventional reactivity of metallaphotoredox catalysis with the unparalleled levels of control offered by enzymes would give a new class of artificial metallaphotoredoxenzymes (PhotoArMs) Herein we investigate the development of novel PhotoArMs based on the biotin-streptavidin technology powered by an external photocatalyst to carry out enantioselective coupling reactions. 1) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw, R. W. Evans and D. W. C. MacMillan, Nat. Rev. Chem. 2017 , 1 , 0052 2) M. Silvi and P. Melchiorre, Nature 2018 , 554 , 41 3) F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M.M. Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J.C. Lewis and T.R. Ward, Chem. Rev. 2018 , 118 , 142
Directed Evolution of Artificial Metalloproteins and Metalloenzymes Research Project | 1 Project MembersArtificial metalloenzymes have emerged as a prolific field of research in the past decade. Such hybrid biosystems result from the incorporation of a metallocofactor within a protein scaffold to endow the macromolecule with novel catalytic properties. Thanks to the progress achieved in recombinant protein expression and evolution, artificial metalloproteins offer an attractive means to complement or substitute natural enzymes. Building on the group's expertize in the design and optimization of artificial metalloenzymes, this proposal sets out develop artificial monooxygenases based on the biotin-streptavidin technology. This work complements our work on C-H activation relying on Rh-based artificial metalloenzymes (Hyster et. al., Science 2012, 338, 500). The field of bioinorganic chemistry has developed a handful of nitrogen-based small coordination compounds containing earth-abundant metals that, in combination with hydrogen peroxide, have been used for the oxidation of hydrocarbons. Building on this, we will prepare a series of iron- and manganese complexes bearing biotinylated tetradentate aminopyridine ligands. Their activity will be screened in the presence of streptavidin. A chemo-genetic optimization strategy will be initially applied to improve the performance of the artificial monooxygenases. For this purpose, a series of model alkanes and alkyl ethers with increasing C-H bond dissociation energies will be screened using a 96-well plate format. Next, it is proposed to implement an E. coli surface display of streptavidin to significantly increase the throughput of the directed evolution effort. Here, we will rely on a fluorescence-activated droplet sorting high-throughput screen using coumarin methyl-ether as pro-fluorescent substrate. With the aim of exploiting artificial monooxygenases for the late-stage functionalization of complex molecules, we will subsequently evolve the regioselectivity of the most promising biohybrids. We anticipate that such systems may offer attractive alternatives to both natural enzymes and small molecule catalysts for the (late-stage) functionalization of inert C-H bonds.
