Dr. Felix Tobola
Hamburg, Hamburg, Deutschland
177 Follower:innen
175 Kontakte
Aktivitäten
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Neben einem schönen Helmut Schmidt-Zitat😁 und autobiographischen Infos zu meiner Vita als Arzt konnte ich im Interview mit Yvonne Scheller von…
Neben einem schönen Helmut Schmidt-Zitat😁 und autobiographischen Infos zu meiner Vita als Arzt konnte ich im Interview mit Yvonne Scheller von…
Beliebt bei Dr. Felix Tobola
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Cell Painting is a multi-parameter image-based description of the cell response to any perturbator condition: treatment with a compounds, a siRNA…
Cell Painting is a multi-parameter image-based description of the cell response to any perturbator condition: treatment with a compounds, a siRNA…
Beliebt bei Dr. Felix Tobola
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Benefits of Attending the 2nd Annual Synthetic Biology Congress - Hear from & meet with the key innovators leading the way in #syntheticbiology…
Benefits of Attending the 2nd Annual Synthetic Biology Congress - Hear from & meet with the key innovators leading the way in #syntheticbiology…
Beliebt bei Dr. Felix Tobola
Berufserfahrung
Ausbildung
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Technische Universität Graz
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Activities and Societies: - Organization of the DocDay: A symposium for PhD students from molecular biosciences in Graz- Organization of the Ig Nobel Price show in Graz
Doctoral Studies of Natural Sciences – Biotechnology, Biochemistry and Food Chemisty
Doktoratskolleg Molecular Enzymology
- Project planning, -management, -execution and -reporting
- Supervision of master students and interns
- PhD thesis “Tuning receptor-ligand interactions by the incorporation of non-canonical amino acids” (grade 1.0) -
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- Internship at the University of Applied Sciences Bremen (Project ModuLES; Development of a microalgae-based life support system for application under microgravitation)
- Master thesis at the Forschungszentrum Jülich: “Engineering of the Corynebacterium glutamicum Transcription Regulator LysG“ (grade: 1.3) -
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- Microbiology
- Genetics research
- Biological oceanography
- Marine biology
- Marine ecosystems -
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- Focus on industrial biotechnology
- Topics: biotechnology, biochemistry, microbiology, genetics, cell biology, immunology and math, among others
- Included a semester and an internship abroad
- Bachelor thesis at the University of Applied Sciences Bremen: „Feasibility study of an algae-bio-refinery – UV-C radiation as a tool for achieving an axenic Chlorella vulgaris culture” (grade: 1.0)
Veröffentlichungen
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One, two, many: Strategies to alter the number of carbohydrate binding sites of lectins
Biotechnology Advances
Carbohydrates are more than an energy-storage. They are ubiquitously found on cells and most proteins, where they encode biological information. Lectins bind these carbohydrates and are essential for translating the encoded information into biological functions and processes. Hundreds of lectins are known, and they are found in all domains of life. For half a century, researchers have been preparing variants of lectins in which the binding sites are varied. In this way, the traits of the…
Carbohydrates are more than an energy-storage. They are ubiquitously found on cells and most proteins, where they encode biological information. Lectins bind these carbohydrates and are essential for translating the encoded information into biological functions and processes. Hundreds of lectins are known, and they are found in all domains of life. For half a century, researchers have been preparing variants of lectins in which the binding sites are varied. In this way, the traits of the lectins such as the affinity, avidity and specificity towards their ligands as well as their biological efficacy were changed. These efforts helped to unravel the biological importance of lectins and resulted in improved variants for biotechnological exploitation and potential medical applications. This review gives an overview on the methods for the preparation of artificial lectins and complexes thereof and how reducing or increasing the number of binding sites affects their function.
Andere Autor:innen -
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Engineering the Ligand Specificity of the Human Galectin-1 by Incorporation of Tryptophan Analogues
ChemBioChem
Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced…
Galectin-1 is a β-galactoside-binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin-1 specificity, we introduced several non-canonical tryptophan analogues at this position of human galectin-1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7-azatryptophan and 7-fluorotryptophan showed a reduced affinity for 3’-sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin-1 is an attractive approach for fine-tuning its interactions with different ligands.
Andere Autor:innen -
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Engineering and application of a biosensor with focused ligand specificity
Nature Communications
Cell factories converting bio-based precursors to chemicals present an attractive avenue to a sustainable economy, yet screening of genetically diverse strain libraries to identify the best-performing whole-cell biocatalysts is a low-throughput endeavor. For this reason, transcriptional biosensors attract attention as they allow the screening of vast libraries when used in combination with fluorescence-activated cell sorting (FACS). However, broad ligand specificity of transcriptional…
Cell factories converting bio-based precursors to chemicals present an attractive avenue to a sustainable economy, yet screening of genetically diverse strain libraries to identify the best-performing whole-cell biocatalysts is a low-throughput endeavor. For this reason, transcriptional biosensors attract attention as they allow the screening of vast libraries when used in combination with fluorescence-activated cell sorting (FACS). However, broad ligand specificity of transcriptional regulators (TRs) often prohibits the development of such ultra-high-throughput screens. Here, we solve the structure of the TR LysG of Corynebacterium glutamicum, which detects all three basic amino acids. Based on this information, we follow a semi-rational engineering approach using a FACS-based screening/counterscreening strategy to generate an l-lysine insensitive LysG-based biosensor. This biosensor can be used to isolate l-histidine-producing strains by FACS, showing that TR engineering towards a more focused ligand spectrum can expand the scope of application of such metabolite sensors.
Andere Autor:innen -
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‘Clickable lectins’: bioorthogonal reactive handles facilitate the directed conjugation of lectins in a modular fashion
Interface Focus
Lectins are carbohydrate-binding proteins with specificity for their target ligands. They play diverse roles in cellular recognition and signalling processes, as well as in infections and cancer metastasis. Owing to their specificity, lectins find application in biotechnology and medicine, e.g. for blood group typing, purification of glycoproteins or lipids and as markers that target cancer cells. For some applications, lectins are immobilized on a solid support, or they are conjugated with…
Lectins are carbohydrate-binding proteins with specificity for their target ligands. They play diverse roles in cellular recognition and signalling processes, as well as in infections and cancer metastasis. Owing to their specificity, lectins find application in biotechnology and medicine, e.g. for blood group typing, purification of glycoproteins or lipids and as markers that target cancer cells. For some applications, lectins are immobilized on a solid support, or they are conjugated with other molecules. Classical protein conjugation reactions at nucleophilic amino acids such as cysteine or lysine are often non-selective, and the site of conjugation is difficult to pre-define. Random conjugation, however, can interfere with protein function. Therefore, we sought to equip lectins with a unique reactive handle, which can be conjugated with other molecules in a pre-defined manner. We site-specifically introduced non-canonical amino acids carrying bioorthogonal reactive groups into several lectins. As a proof of principle, we conjugated these ‘clickable lectins’ with small molecules. Furthermore, we conjugated lectins with different ligand specificities with one another to produce superlectins. The ‘clickable lectins’ might be useful for any process where lectins shall be conjugated with another module in a selective, pre-defined and site-specific manner.
Andere Autor:innenVeröffentlichung anzeigen -
Effect of non-canonical amino acids on protein-carbohydrate interactions: Structure, dynamics and carbohydrate affinity of a lectin engineered with fluorinated tryptophan analogs.
ACS Chemical Biology
Protein-carbohydrate interactions play crucial roles in biology. Understanding and modifying these interactions is of major interest for fighting many diseases. We took a synthetic biology approach and incorporated non-canonical amino acids into a bacterial lectin to modulate its interactions with carbohydrates. We focused on tryptophan that is prevalent in carbohydrate binding sites. The exchange of the tryptophan residues with analogs fluorinated at different positions resulted in three…
Protein-carbohydrate interactions play crucial roles in biology. Understanding and modifying these interactions is of major interest for fighting many diseases. We took a synthetic biology approach and incorporated non-canonical amino acids into a bacterial lectin to modulate its interactions with carbohydrates. We focused on tryptophan that is prevalent in carbohydrate binding sites. The exchange of the tryptophan residues with analogs fluorinated at different positions resulted in three distinctly fluorinated variants of the lectin from Ralstonia solanacearum. We observed differences in stability and affinity towards fucosylated glycans and rationalized them by X-ray and modeling studies. While fluorination decreased the aromaticity of the indole ring and, therefore, the strength of carbohydrate-aromatic interactions, additional weak hydrogen bonds were formed between fluorine and the ligand hydroxyl groups. Our approach opens new possibilities to engineer carbohydrate receptors.
Andere Autor:innen -
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Systems biocatalysis: para-alkenylation of unprotected phenols
Catalysis Science & Technology
Commercially available phenol derivatives were transformed with pyruvate to form a new C–C bond leading to the corresponding para-coumaric acids and only one molecule of water as an innocent side product in buffer. The reaction was catalysed by a biocatalytic system consisting of two enzymatic steps, which were run simultaneously: (i) in the first step catalysed by a tyrosine phenol lyase the C–C coupling of phenol derivatives with pyruvate and ammonia yielded L-tyrosine derivatives, (ii) which…
Commercially available phenol derivatives were transformed with pyruvate to form a new C–C bond leading to the corresponding para-coumaric acids and only one molecule of water as an innocent side product in buffer. The reaction was catalysed by a biocatalytic system consisting of two enzymatic steps, which were run simultaneously: (i) in the first step catalysed by a tyrosine phenol lyase the C–C coupling of phenol derivatives with pyruvate and ammonia yielded L-tyrosine derivatives, (ii) which were transformed in the second step to the final product via ammonia elimination catalysed by a tyrosine ammonia lyase. The reactions proceeded with exquisite regio- and stereoselectivity yielding just the para-products with the (E)-configuration. The method represents an efficient approach for the direct alkenylation of phenols on a preparative scale (up to 0.6 mmol) affording (E)-para-coumaric acids in excellent isolated yields without requiring chromatographic purification. Co-expression of the involved enzymes in a single host gave access to single catalyst preparation.
Andere Autor:innen -
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Pichia anomala 29X: a resistant strain for lignocellulosic biomass hydrolysate fermentation
FEMS Yeast Research
To efficiently use lignocellulosic biomass hydrolysates as fermentation media for bioethanol production, besides being capable of producing significant amount of ethanol, the fermenting host should also meet the following two requirements: (1) resistant to the inhibitory compounds formed during biomass pretreatment process, (2) capable of utilizing C5 sugars, such as xylose, as carbon source. In our laboratory, a screening was conducted on microorganisms collected from environmental sources for…
To efficiently use lignocellulosic biomass hydrolysates as fermentation media for bioethanol production, besides being capable of producing significant amount of ethanol, the fermenting host should also meet the following two requirements: (1) resistant to the inhibitory compounds formed during biomass pretreatment process, (2) capable of utilizing C5 sugars, such as xylose, as carbon source. In our laboratory, a screening was conducted on microorganisms collected from environmental sources for their tolerance to hydrolysate inhibitors. A unique resistant strain was selected and identified as Pichia anomala (Wickerhamomyces anomalus), deposited as CBS 132101. The strain is able to produce ethanol in various biomass hydrolysates, both with and without oxygen. Besides, the strain could assimilate xylose and use nitrate as N source. These physiological characteristics make P. anomala an interesting strain for bioethanol production from lignocellulosic biomass hydrolysates.
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Kurse
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Fundamental and Applied Research: Third-Party Funding, Grant Proposals, Collaboration, Resources, and Impact
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Project Management
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The World of Intellectual Property Rights
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Sprachen
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Deutsch
Muttersprache oder zweisprachig
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Englisch
Verhandlungssicher
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Französisch
Grundkenntnisse
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Niederländisch
Grundkenntnisse
Weitere Aktivitäten von Dr. Felix Tobola
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We just published a series of clickable lectins carrying bioorthogonal reactive groups, with which these can be conjugated with one…
We just published a series of clickable lectins carrying bioorthogonal reactive groups, with which these can be conjugated with one…
Veröffentlicht von Dr. Felix Tobola
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If you care about climate change, deforestation and world hunger, can you please take a moment to reflect on your opinion about GMO foods? Last…
If you care about climate change, deforestation and world hunger, can you please take a moment to reflect on your opinion about GMO foods? Last…
Beliebt bei Dr. Felix Tobola
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Last night in Brussels: SenseUP won the first price of the EARTO Award, category: impact expected. At SenseUP we develop biosensors, which make…
Last night in Brussels: SenseUP won the first price of the EARTO Award, category: impact expected. At SenseUP we develop biosensors, which make…
Beliebt bei Dr. Felix Tobola