Molecular Bionics (Seebeck)Head of Research Unit Prof. Dr.Florian Peter SeebeckOverviewMembersPublicationsProjects & CollaborationsProjects & Collaborations OverviewMembersPublicationsProjects & Collaborations Projects & Collaborations 12 foundShow per page10 10 20 50 Late-stage tritium labelling of therapeutic oligonucleotides via methyl transferases Research Project | 1 Project MembersImported from Grants Tool 4643145 Diversity-oriented biocatalytic production of complex polyamines Research Project | 1 Project MembersNo Description available Development of enzymes and reagents for alkylation and ligation reactions under physiological conditions Research Project | 1 Project MembersNo Description available Evolutionary and energetic landscapes of enzyme catalyzed oxidative sulfur transfers Research Project | 4 Project MembersSulfur containing metabolites are ubiquitous and important factors in all life forms. Deciphering their physiological functions, their chemical reactivity and their biosynthetic origins has proven a productive avenue to identify causes and remedies of human disease, to understand microbial contributions and reactions to climate change, and to recognize fundamental patterns of molecular evolutions. The discovery and description of sulfur-related biochemistry also provides important impulses for biotechnological innovation. In this very active field we plan to pursue the following key aims: 1) Mechanistic characterization of enzymes that mediate oxidative carbon-sulfur transfers. 2) Prospecting the landscape of EGT biosynthesis. 3) Description of a novel class of sulfur metabolites. 4) Characterisation of the catalytic mechanism of the formylglycine generating enzyme. MetTraC Research Project | 1 Project MembersThe goal of this project is to develop a general system for preparative enzyme-catalyzed methylation reactions. Selective methylation of complex molecules can be challenging for synthetic chemistry. Given the exquisite chemo-, regio- and stereoselectivities of enzyme catalysis we believe that biocatalysis presents a powerful alternative for commercial production of pharmaceuticals and fine chemicals. In this project we demonstrate the applicability and commercial viability of a novel enzyme-based technology to preparative methylation reactions. Construction of a simple S- adenosylmethionine regeneration system for preparative enzyme catalyzed methylation Research Project | 1 Project MembersThe third wave of biocatalysis has established the versatility of in vitro reconstituted enzyme cascades for the production of market-relevant organics. Enzymes that catalyze group transfers to and from complex molecules are of particular interest because such reactions are often challenging to achieve by chemical means. For example, S-adenosylmethionine (SAM) dependent methyltransferases (MTs) can methylate natural products with exquisite regio-, chemo- and stereoselectivity. Given the large number of known MTs with defined substrate specificities, the even larger number of putative MTs annotated in todays genome data bases, combined with the increasing possibilities to redesign substrate specificities of enzymes by computational design, it seems possible to engineer biocatalytic solutions for any preparative methylation reaction. Currently the biotechnological application of MTs is limited due to the very high costs of the stoichiometric methyl donor SAM. To mitigate this problem we plan to develop a simple catalytic system for in situ regeneration of SAM. Development of a synthetic pathway for production of a high value added natural product Research Project | 1 Project MembersWe retrosynthetically designed a pathway along a completely novel set of new-to-nature metabolites for the synthesis of a high-value-added product currently. The pathway will be implemented using rational design approaches complemented by advanced high throughput screening methods for the reprogramming of the substrate specificities of known enzymes. Biosynthesis selenometabolites Research Project | 1 Project MembersHeavy metals, electrophilic toxins and reactive oxygen species are common stressors of cellular live and are the cause of many human health problems such as mental disorder, inflammatory disease and numerous cancers. Plants and microorganisms are vulnerable to the same chemical stressors, but some of these species have acquired remarkable resilience that allows them to strife under very hostile conditions. Elucidation of the underlying mechanisms may provide novel strategies for therapeutic interventions in metal- or redox-induced medical disorders. Sulfur and selenium containing small molecules are key components of cellular defence systems against chemical stress. Microbial resistance to extreme stress often relies on unusual small molecules with remarkable properties. In this project we will investigate the biosynthetic origin and physiological role of a seleno-compound produced by the plant associated bacterium Variovorax paradoxus . This metabolite is also present in humans, but its physiological effects are largely unknown ErgOX - Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersOxidative stress causes cancer, cardiovascular, neurodegenerative and infective disease. Much of cellular oxidative stress is mediated, communicated, mitigated or amplified by a complex system of sulfur containing small metabolites or protein-based cysteines. Characterization of key players and reactions in this network is crucial for preventive and therapeutic interventions. I propose a new perspective on sulfur biochemistry. The reactivity of sulfur with the oxidative stressors superoxide, peroxides or hydroxyl radicals is well established, but far less is known about reactions between sulfur and molecular oxygen. I shall demonstrate that this reaction is fundamental to cellular life, and how advances in this field provide new options in medicine, biotechnology and the food industry. Assisted by a team of three PhD students and a postdoctoral researcher I intend to establish this new research field by identification, characterization and engineering of enzymatic activities which catalyse oxidative carbon-sulfur bond formation and cleavage. Specific systems in this study include the biosynthetic enzymes for ergothioneine which is a sulfur containing secondary metabolite with potent activities on cellular functions. Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersSulfur containing secondary metabolites are prime modulators of the redox and metal homeostasis in microbial as well as human cells and therefore play important roles in many medical disorders. The identification of novel biothiols and investigation of their biosynthesis physiological functions has gained much interest in the last few years. 3-6 . The enzymology of sulfur incorporation for many of these compounds is not clear and suggesting that much of C-S bond forming biocatalysis is yet to be discovered. 12 12 OverviewMembersPublicationsProjects & Collaborations
Projects & Collaborations 12 foundShow per page10 10 20 50 Late-stage tritium labelling of therapeutic oligonucleotides via methyl transferases Research Project | 1 Project MembersImported from Grants Tool 4643145 Diversity-oriented biocatalytic production of complex polyamines Research Project | 1 Project MembersNo Description available Development of enzymes and reagents for alkylation and ligation reactions under physiological conditions Research Project | 1 Project MembersNo Description available Evolutionary and energetic landscapes of enzyme catalyzed oxidative sulfur transfers Research Project | 4 Project MembersSulfur containing metabolites are ubiquitous and important factors in all life forms. Deciphering their physiological functions, their chemical reactivity and their biosynthetic origins has proven a productive avenue to identify causes and remedies of human disease, to understand microbial contributions and reactions to climate change, and to recognize fundamental patterns of molecular evolutions. The discovery and description of sulfur-related biochemistry also provides important impulses for biotechnological innovation. In this very active field we plan to pursue the following key aims: 1) Mechanistic characterization of enzymes that mediate oxidative carbon-sulfur transfers. 2) Prospecting the landscape of EGT biosynthesis. 3) Description of a novel class of sulfur metabolites. 4) Characterisation of the catalytic mechanism of the formylglycine generating enzyme. MetTraC Research Project | 1 Project MembersThe goal of this project is to develop a general system for preparative enzyme-catalyzed methylation reactions. Selective methylation of complex molecules can be challenging for synthetic chemistry. Given the exquisite chemo-, regio- and stereoselectivities of enzyme catalysis we believe that biocatalysis presents a powerful alternative for commercial production of pharmaceuticals and fine chemicals. In this project we demonstrate the applicability and commercial viability of a novel enzyme-based technology to preparative methylation reactions. Construction of a simple S- adenosylmethionine regeneration system for preparative enzyme catalyzed methylation Research Project | 1 Project MembersThe third wave of biocatalysis has established the versatility of in vitro reconstituted enzyme cascades for the production of market-relevant organics. Enzymes that catalyze group transfers to and from complex molecules are of particular interest because such reactions are often challenging to achieve by chemical means. For example, S-adenosylmethionine (SAM) dependent methyltransferases (MTs) can methylate natural products with exquisite regio-, chemo- and stereoselectivity. Given the large number of known MTs with defined substrate specificities, the even larger number of putative MTs annotated in todays genome data bases, combined with the increasing possibilities to redesign substrate specificities of enzymes by computational design, it seems possible to engineer biocatalytic solutions for any preparative methylation reaction. Currently the biotechnological application of MTs is limited due to the very high costs of the stoichiometric methyl donor SAM. To mitigate this problem we plan to develop a simple catalytic system for in situ regeneration of SAM. Development of a synthetic pathway for production of a high value added natural product Research Project | 1 Project MembersWe retrosynthetically designed a pathway along a completely novel set of new-to-nature metabolites for the synthesis of a high-value-added product currently. The pathway will be implemented using rational design approaches complemented by advanced high throughput screening methods for the reprogramming of the substrate specificities of known enzymes. Biosynthesis selenometabolites Research Project | 1 Project MembersHeavy metals, electrophilic toxins and reactive oxygen species are common stressors of cellular live and are the cause of many human health problems such as mental disorder, inflammatory disease and numerous cancers. Plants and microorganisms are vulnerable to the same chemical stressors, but some of these species have acquired remarkable resilience that allows them to strife under very hostile conditions. Elucidation of the underlying mechanisms may provide novel strategies for therapeutic interventions in metal- or redox-induced medical disorders. Sulfur and selenium containing small molecules are key components of cellular defence systems against chemical stress. Microbial resistance to extreme stress often relies on unusual small molecules with remarkable properties. In this project we will investigate the biosynthetic origin and physiological role of a seleno-compound produced by the plant associated bacterium Variovorax paradoxus . This metabolite is also present in humans, but its physiological effects are largely unknown ErgOX - Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersOxidative stress causes cancer, cardiovascular, neurodegenerative and infective disease. Much of cellular oxidative stress is mediated, communicated, mitigated or amplified by a complex system of sulfur containing small metabolites or protein-based cysteines. Characterization of key players and reactions in this network is crucial for preventive and therapeutic interventions. I propose a new perspective on sulfur biochemistry. The reactivity of sulfur with the oxidative stressors superoxide, peroxides or hydroxyl radicals is well established, but far less is known about reactions between sulfur and molecular oxygen. I shall demonstrate that this reaction is fundamental to cellular life, and how advances in this field provide new options in medicine, biotechnology and the food industry. Assisted by a team of three PhD students and a postdoctoral researcher I intend to establish this new research field by identification, characterization and engineering of enzymatic activities which catalyse oxidative carbon-sulfur bond formation and cleavage. Specific systems in this study include the biosynthetic enzymes for ergothioneine which is a sulfur containing secondary metabolite with potent activities on cellular functions. Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersSulfur containing secondary metabolites are prime modulators of the redox and metal homeostasis in microbial as well as human cells and therefore play important roles in many medical disorders. The identification of novel biothiols and investigation of their biosynthesis physiological functions has gained much interest in the last few years. 3-6 . The enzymology of sulfur incorporation for many of these compounds is not clear and suggesting that much of C-S bond forming biocatalysis is yet to be discovered. 12 12
Late-stage tritium labelling of therapeutic oligonucleotides via methyl transferases Research Project | 1 Project MembersImported from Grants Tool 4643145
Diversity-oriented biocatalytic production of complex polyamines Research Project | 1 Project MembersNo Description available
Development of enzymes and reagents for alkylation and ligation reactions under physiological conditions Research Project | 1 Project MembersNo Description available
Evolutionary and energetic landscapes of enzyme catalyzed oxidative sulfur transfers Research Project | 4 Project MembersSulfur containing metabolites are ubiquitous and important factors in all life forms. Deciphering their physiological functions, their chemical reactivity and their biosynthetic origins has proven a productive avenue to identify causes and remedies of human disease, to understand microbial contributions and reactions to climate change, and to recognize fundamental patterns of molecular evolutions. The discovery and description of sulfur-related biochemistry also provides important impulses for biotechnological innovation. In this very active field we plan to pursue the following key aims: 1) Mechanistic characterization of enzymes that mediate oxidative carbon-sulfur transfers. 2) Prospecting the landscape of EGT biosynthesis. 3) Description of a novel class of sulfur metabolites. 4) Characterisation of the catalytic mechanism of the formylglycine generating enzyme.
MetTraC Research Project | 1 Project MembersThe goal of this project is to develop a general system for preparative enzyme-catalyzed methylation reactions. Selective methylation of complex molecules can be challenging for synthetic chemistry. Given the exquisite chemo-, regio- and stereoselectivities of enzyme catalysis we believe that biocatalysis presents a powerful alternative for commercial production of pharmaceuticals and fine chemicals. In this project we demonstrate the applicability and commercial viability of a novel enzyme-based technology to preparative methylation reactions.
Construction of a simple S- adenosylmethionine regeneration system for preparative enzyme catalyzed methylation Research Project | 1 Project MembersThe third wave of biocatalysis has established the versatility of in vitro reconstituted enzyme cascades for the production of market-relevant organics. Enzymes that catalyze group transfers to and from complex molecules are of particular interest because such reactions are often challenging to achieve by chemical means. For example, S-adenosylmethionine (SAM) dependent methyltransferases (MTs) can methylate natural products with exquisite regio-, chemo- and stereoselectivity. Given the large number of known MTs with defined substrate specificities, the even larger number of putative MTs annotated in todays genome data bases, combined with the increasing possibilities to redesign substrate specificities of enzymes by computational design, it seems possible to engineer biocatalytic solutions for any preparative methylation reaction. Currently the biotechnological application of MTs is limited due to the very high costs of the stoichiometric methyl donor SAM. To mitigate this problem we plan to develop a simple catalytic system for in situ regeneration of SAM.
Development of a synthetic pathway for production of a high value added natural product Research Project | 1 Project MembersWe retrosynthetically designed a pathway along a completely novel set of new-to-nature metabolites for the synthesis of a high-value-added product currently. The pathway will be implemented using rational design approaches complemented by advanced high throughput screening methods for the reprogramming of the substrate specificities of known enzymes.
Biosynthesis selenometabolites Research Project | 1 Project MembersHeavy metals, electrophilic toxins and reactive oxygen species are common stressors of cellular live and are the cause of many human health problems such as mental disorder, inflammatory disease and numerous cancers. Plants and microorganisms are vulnerable to the same chemical stressors, but some of these species have acquired remarkable resilience that allows them to strife under very hostile conditions. Elucidation of the underlying mechanisms may provide novel strategies for therapeutic interventions in metal- or redox-induced medical disorders. Sulfur and selenium containing small molecules are key components of cellular defence systems against chemical stress. Microbial resistance to extreme stress often relies on unusual small molecules with remarkable properties. In this project we will investigate the biosynthetic origin and physiological role of a seleno-compound produced by the plant associated bacterium Variovorax paradoxus . This metabolite is also present in humans, but its physiological effects are largely unknown
ErgOX - Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersOxidative stress causes cancer, cardiovascular, neurodegenerative and infective disease. Much of cellular oxidative stress is mediated, communicated, mitigated or amplified by a complex system of sulfur containing small metabolites or protein-based cysteines. Characterization of key players and reactions in this network is crucial for preventive and therapeutic interventions. I propose a new perspective on sulfur biochemistry. The reactivity of sulfur with the oxidative stressors superoxide, peroxides or hydroxyl radicals is well established, but far less is known about reactions between sulfur and molecular oxygen. I shall demonstrate that this reaction is fundamental to cellular life, and how advances in this field provide new options in medicine, biotechnology and the food industry. Assisted by a team of three PhD students and a postdoctoral researcher I intend to establish this new research field by identification, characterization and engineering of enzymatic activities which catalyse oxidative carbon-sulfur bond formation and cleavage. Specific systems in this study include the biosynthetic enzymes for ergothioneine which is a sulfur containing secondary metabolite with potent activities on cellular functions.
Enzymology of oxidative sulfur transfers Research Project | 1 Project MembersSulfur containing secondary metabolites are prime modulators of the redox and metal homeostasis in microbial as well as human cells and therefore play important roles in many medical disorders. The identification of novel biothiols and investigation of their biosynthesis physiological functions has gained much interest in the last few years. 3-6 . The enzymology of sulfur incorporation for many of these compounds is not clear and suggesting that much of C-S bond forming biocatalysis is yet to be discovered.
