A5037318456- Microbial Natural Products and Biosynthesis
- Alkaloids: synthesis and pharmacology
- Algal biology and biofuel production
- Marine Sponges and Natural Products
- Plant biochemistry and biosynthesis
- Natural product bioactivities and synthesis
- Photosynthetic Processes and Mechanisms
- Advanced Synthetic Organic Chemistry
- Metabolomics and Mass Spectrometry Studies
- Protist diversity and phylogeny
- Biochemical and Structural Characterization
- Catalytic C–H Functionalization Methods
- Chemical Synthesis and Analysis
- Biocrusts and Microbial Ecology
- Sulfur-Based Synthesis Techniques
- Synthesis and Catalytic Reactions
- Synthesis and Biological Activity
- Synthetic Organic Chemistry Methods
- Microbial Metabolism and Applications
- European Socioeconomic and Political Studies
- Asymmetric Synthesis and Catalysis
- Click Chemistry and Applications
- Genomics and Phylogenetic Studies
- Bioactive Compounds and Antitumor Agents
- Cancer therapeutics and mechanisms
University of Bonn
2022-2025
University of Potsdam
2018-2023
Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI)
2012-2017
Leibniz Institute for Neurobiology
2014-2015
Leibniz Association
2012-2014
Ludwig-Maximilians-Universität München
1998
Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative systematically document links between metabolome (meta)genome data, aiding identification of natural product biosynthetic origins structures.
Abstract Specialized or secondary metabolites are small molecules of biological origin, often showing potent activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis these natural products is governed by sets co-regulated physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs a standardized machine-readable way, Minimum Information Biosynthetic Gene cluster (MIBiG) data standard repository was initiated...
Getting indole terpenes into shape: Genetic analysis, pathway dissection, and heterologous reconstitution provide first insights bacterial indolosesquiterpenoid biosynthesis unveil the involvement of a new type terpene cyclase an oxygenase in formation indosespene, xiamycin, sespenine ring systems. Furthermore, expression led to discovery CC- CN-linked xiamycin dimers. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but...
Abstract The first total synthesis of sespenine, a rare indole sesquiterpenoid from mangrove endophyte, has been accomplished. A bioinspired aza‐Prins/Friedel–Crafts/retro Friedel–Crafts cascade reaction assembles the bridged tetrahydroquinoline core. Further investigations on aza‐Prins cyclization imply that C3 configuration hydroxyindolenine intermediate is crucial to biosynthesis sespenine and its congener xiamycin A.
Radical diversification: Through the discovery of diverse indolosesquiterpene dimers in a strain heterologously expressing xiamycin biosynthesis genes, analysis mutants, and biotransformation studies, it has been inferred that single flavoprotein mediates NC NN aryl coupling reactions, as well formation cyclic ether (oxiamycin). Synthetic emulation this unusual transformation provides evidence for radical-based mechanism.
Abstract Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of flexible biosynthetic machineries that correlates with stunning structural diversity NRPs is poorly understood. Here, we show recombination a key driver bacterial NRP synthetase (NRPS) genes across distant phyla, which has guided diversification plethora families by extensive mixing matching biosynthesis genes. The systematic dissection...
Sulfa drugs, such as sulfonilamide and dapsone, are classical antibiotics that have been in clinical use worldwide. Despite the relatively simple architectures, practically no natural products known to feature aromatic sulfonamide or diarylsulfone substructures. We report unexpected discovery of three fully unprecedented, sulfonyl-bridged alkaloid dimers (sulfadixiamycins A-C) from recombinant Streptomyces species harboring entire xiamycin biosynthesis gene cluster. Sulfadixiamycins exhibit...
Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet majority biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis secondary metabolite expression in model strain Nostoc punctiforme PCC73102 using RNA-seq fluorescence reporter analysis. Our data demonstrate that cryptic not silent but expressed with regular or sporadic pattern....
Graphical Abstract [3+2] in the wild: Biomimetic natural product syntheses and theoretical considerations have indicated that 1,3-dipolar cycloadditions take place nature. Now, structure, biosynthesis, function of a heavily modified prenylated flavin cofactor been elucidated. In azomethine ylide form, it undergoes with aromatic acids promotes their decarboxylation.
Abstract The first total synthesis of sespenine, a rare indole sesquiterpenoid from mangrove endophyte, has been accomplished. A bioinspired aza‐Prins/Friedel–Crafts/retro Friedel–Crafts cascade reaction assembles the bridged tetrahydroquinoline core. Further investigations on aza‐Prins cyclization imply that C3 configuration hydroxyindolenine intermediate is crucial to biosynthesis sespenine and its congener xiamycin A.
Modular megasynthases, such as polyketide synthases (PKSs) and non‐ribosomal peptide synthetases (NRPSs), are molecular assembly lines that biosynthesize many pharmaceutically ecologically important natural products. Understanding how these compounds evolve could inspire the artificial evolution of compound diversity by metabolic engineering. Over past two decades, a number seminal studies have significantly contributed to our understanding product evolution. However, NRPS PKS remains poorly...
Modular megasynthases, such as polyketide synthases (PKSs) and non‐ribosomal peptide synthetases (NRPSs), are molecular assembly lines that biosynthesize many pharmaceutically ecologically important natural products. Understanding how these compounds evolve could inspire the artificial evolution of compound diversity by metabolic engineering. Over past two decades, a number seminal studies have significantly contributed to our understanding product evolution. However, NRPS PKS remains poorly...
Indolterpene in Form gebracht: Genanalyse, Aufklärung der Biosynthesepfade und heterologe Rekonstitution liefern erste Einblicke die bakterielle Indolosesquiterpenoid-Biosynthese deuten auf Beteiligung einer neuartigen Terpencyclase Indoloxygenase beim Aufbau von Indosespen-, Xiamycin- Sespenin-Ringsystemen hin. Im Zuge heterologen Exprimierungsstudie wurden darüber hinaus C-C- C-N-verknüpfte Xiamycin-Dimere entdeckt.
Abstract Divergolides are structurally diverse ansamycins produced by a bacterial endophyte ( Streptomyces sp.) of the mangrove tree Bruguiera gymnorrhiza . By genomic analyses gene locus coding for divergolide pathway was detected. The div cluster encodes genes biosynthesis 3‐amino‐5‐hydroxybenzoate and rare extender units ethylmalonyl‐CoA isobutylmalonyl‐CoA, polyketide assembly modular type I synthase (PKS), enzymes involved in tailoring reactions, such as Baeyer–Villiger oxygenase. A...
A ten-step (the longest linear sequence) total synthesis of sespenine was accomplished.
Abstract Cyclisierungsreaktionen von Terpenen und Terpenoiden zählen zu den komplexesten chemischen Reaktionen in der Natur tragen maßgeblich zur enormen Strukturvielfalt dieser größten Naturstofffamilie bei. Zahlreiche Studien auf chemischer, genetischer biochemischer Ebene wurden durchgeführt, um mechanistische Einblicke diese faszinierenden erlangen, die Terpen‐ Terpenoid‐Cyclasen katalysiert werden. Eine Vielzahl Enzyme konnte seither charakterisiert Nach klassischer Lehrbuchmeinung...
Abstract Terpenoid natural products comprise a wide range of molecular architectures that typically result from C–C bond formations catalysed by classical type I/II terpene cyclases. However, the diversity biologically active terpenoids is substantially increased fully unrelated, non-canonical terpenoid Their evolutionary origin has remained enigmatic. Here we report in vitro reconstitution an unusual flavin-dependent bacterial indoloterpenoid cyclase, XiaF, together with designated...
Radikale Diversifizierung. Die Entdeckung diverser Indolosesquiterpen-Dimere durch heterologe Expression des Xiamycin-Biosynthese-Genclusters, Mutantenanalyse und Biotransformationen impliziert, dass ein einzelnes Flavoprotein N-C- N-N-Arylkupplungen sowie die Bildung eines cyclischen Ethers (Oxiamycin) vermittelt. biomimetische Synthese liefert Hinweise auf einen radikalabhängigen Mechanismus.
Genomes of cyanobacteria feature a variety cryptic biosynthetic pathways for complex natural products, but the peculiarities limiting discovery and exploitation metabolic dark matter are not well understood. Here we describe two cell density-dependent chemical mediators, nostoclide nostovalerolactone, in symbiotic model strain Nostoc punctiforme, demonstrate their pronounced impact on regulation specialized metabolism. Through transcriptional, bioinformatic labeling studies assigned adjacent...
Growth from spores activated a biosynthetic gene cluster in Actinomadura sp. RB29, resulting the identification of two novel groups halogenated polyketide natural products, named maduralactomycins and actinospirols. The unique tetracyclic spirocyclic structures were assigned based on combination NMR analysis, chemoinformatic calculations, X-ray crystallography, 13C labeling studies. On basis HRMS2 data, genome mining, expression studies, we propose an underlying noncanonical angucycline...
[3+2] in freier Wildbahn: Biomimetische Naturstoffsynthesen und theoretische Überlegungen deuteten darauf hin, dass 1,3-dipolare Cycloadditionen der Natur ablaufen. Nun wurde die Struktur, Biosynthese Funktion eines stark modifizierten, prenylierten Flavin-Kofaktors aufgeklärt. In Form Azomethin-Ylids nimmt er an [3+2]-Cycloadditionen mit aromatischen Säuren teil vermittelt deren Decarboxylierung. As a service to our authors and readers, this journal provides supporting information supplied...
Microviridins are a prominent family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) featuring characteristic lactone lactam rings. Their unusual cage-like architecture renders them highly potent serine protease inhibitors which individual variants specifically inhibit different types proteases pharmacological interest. While posttranslational modifications key for the stability bioactivity RiPPs, additional attractive properties can be introduced by functional...