A5066273209- Tryptophan and brain disorders
- Enzyme Catalysis and Immobilization
- Click Chemistry and Applications
- Amino Acid Enzymes and Metabolism
- Cyclopropane Reaction Mechanisms
- Synthesis and Catalytic Reactions
- Vanadium and Halogenation Chemistry
- Catalytic Cross-Coupling Reactions
- Chemical Synthesis and Analysis
- Fluorine in Organic Chemistry
- Metal-Catalyzed Oxygenation Mechanisms
- bioluminescence and chemiluminescence research
- Biofuel production and bioconversion
- Bacterial Genetics and Biotechnology
- Microbial Natural Products and Biosynthesis
- Chemical synthesis and alkaloids
- Erythrocyte Function and Pathophysiology
- Enzyme Production and Characterization
- Microbial Metabolic Engineering and Bioproduction
- Protist diversity and phylogeny
- Innovation, Technology, and Society
- Microbial bioremediation and biosurfactants
- Alkaloids: synthesis and pharmacology
- Innovative Microfluidic and Catalytic Techniques Innovation
- Advanced biosensing and bioanalysis techniques
Bielefeld University
2016-2022
California Institute of Technology
2017
Catalytic anti-Markovnikov oxidation of alkene feedstocks could simplify synthetic routes to many important molecules and solve a long-standing challenge in chemistry. Here we report the engineering cytochrome P450 enzyme by directed evolution catalyze metal-oxo-mediated styrenes with high efficiency. The uses dioxygen as terminal oxidant achieves selectivity for over kinetically favored epoxidation trapping high-energy intermediates catalyzing an oxo transfer, including enantioselective...
Abstract Biocatalytic halogenation with tryptophan halogenases is hampered by severe limitations such as low activity and stability. These drawbacks can be overcome directed evolution, but for screening large mutant libraries, a facile high‐throughput method required. Therefore, we developed quantitative halogenase assay based on Suzuki–Miyaura cross‐coupling towards the formation of fluorescent aryltryptophan. The technique was optimized application in crude E. coli lysate without...
Abstract The combination of the biocatalytic halogenation l ‐tryptophan with subsequent chemocatalytic Suzuki–Miyaura cross‐coupling reactions leads to modular synthesis an array C5, C6, or C7 aryl‐substituted tryptophan derivatives. In a three‐step one‐pot reaction, bromo substituent is initially incorporated regioselectively by immobilized 5‐, 6‐, 7‐halogenases, respectively, concomitant cofactor regeneration. proceeds in aqueous media at room temperature presence NaBr and O 2 . After...
Flavin-dependent halogenases increasingly attract attention as biocatalysts in organic synthesis, facilitating environmentally friendly halogenation strategies that require only FADH2, oxygen, and halide salts. Different flavin-dependent tryptophan regioselectively chlorinate or brominate trypto-phan's indole moiety at C5, C6, C7. Here, we present the first substrate-bound structure of a 6-halogenase, namely Thal, also known ThdH, from bacterium Streptomyces albogriseolus 2.55 Å resolution....
Abstract Halogenases are valuable biocatalysts for selective C−H activation, but despite recent efforts to broaden their application scope by means of protein engineering, improvement thermostability and catalytic efficiency is still desired. A directed evolution campaign aimed at generating a thermostable flavin‐dependent tryptophan 6‐halogenase with reasonable activity suitable chemoenzymatic purposes. These characteristics were tackled combining successive rounds epPCR along semi‐rational...
Abstract Halogenating enzymes are able to introduce halogen substituents under ambient conditions using non‐hazardous reagents with intriguing selectivity, which is highly desired in green chemistry. Although C−H functionalization such as halogenation a well‐known transformation synthetic chemistry, the selective incorporation of halogens conventional chemical approaches often remains challenging. Therefore, enzyme‐based strategies have been emerging valuable alternatives recent years....
Abstract Die Anwendung von Tryptophan‐Halogenasen für die enzymatische Halogenierung hat noch gravierende Limitierungen. Diese könnten mittels gerichteter Evolution überwunden werden, jedoch bedarf Durchmusterung großer Mutantenbibliotheken eines robusten Hochdurchsatz‐fähigen Testsystems. Im Hinblick darauf wurde eine Suzuki‐Miyaura‐Kreuzkupplung als quantitativer Halogenase‐Assay auf Basis der Bildung fluoreszierenden Aryltryptophans entwickelt. Methode im E.‐coli‐Lysat ohne intermediäre...
The late-stage site-selective derivatisation of peptides has many potential applications in structure-activity relationship studies and postsynthetic modification or conjugation bioactive compounds. development orthogonal methods for C-H functionalisation is crucial such peptide derivatisation. Among them, biocatalytic are increasingly attracting attention. Tryptophan halogenases emerged as valuable catalysts to functionalise tryptophan (Trp), while direct enzyme-catalysed halogenation...
Bei der gerichteten Evolution von Halogenasen ist die Identifizierung verbesserter Mutanten aus einer umfangreichen Bibliothek vergleichbar mit Suche nach Nadel im Heuhaufen. In Zuschrift auf S. 14365 ff. nutzen N. Sewald et al. eine Pd-katalysierte Kreuzkupplung beim Hochdurchsatz-Screening Halogenasen. Dank fluorogenen und Bildung eines fluoreszierenden Aryltryptophans fanden Autoren thermostabile Tryptophan-6-Halogenase.