A5032497218- Microbial Natural Products and Biosynthesis
- Carbohydrate Chemistry and Synthesis
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Actinomycetales infections and treatment
- Genomics and Phylogenetic Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Marine Sponges and Natural Products
- Plant biochemistry and biosynthesis
- Vanadium and Halogenation Chemistry
- Porphyrin and Phthalocyanine Chemistry
- Infectious Diseases and Mycology
- Glycosylation and Glycoproteins Research
- Microbial Metabolic Engineering and Bioproduction
- RNA and protein synthesis mechanisms
- Enzyme Catalysis and Immobilization
- Chemical Synthesis and Analysis
- Cancer therapeutics and mechanisms
- Enzyme Production and Characterization
- Pharmacogenetics and Drug Metabolism
- Peptidase Inhibition and Analysis
- Biochemical and Structural Characterization
- Click Chemistry and Applications
- Nanofabrication and Lithography Techniques
- vaccines and immunoinformatics approaches
Leipzig University
2021-2025
Drug Discovery Laboratory (Norway)
2025
University of Tübingen
2013-2023
University Hospital Leipzig
2023
German Center for Infection Research
2013-2022
Scripps Institution of Oceanography
2012-2015
University of California, San Diego
2012-2014
University of Stuttgart
2005-2006
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded biosynthetic gene clusters. Information about these clusters, is currently dispersed throughout the literature, making it difficult exploit. To facilitate consistent systematic deposition retrieval data on we propose Minimum a Biosynthetic Gene cluster (MIBiG) standard.
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.
Meroterpenoids are mixed polyketide-terpenoid natural products with a broad range of biological activities. Herein, we present the structures four new meroterpenoid antibiotics, merochlorins A-D, produced by marine bacterium Streptomyces sp. strain CNH-189, which possess novel chemical skeletons unrelated to known bacterial agents. Draft genome sequencing, mutagenesis, and heterologous biosynthesis in genome-minimized model actinomycete coelicolor provided 57.6 kb merochlorin gene cluster...
Abstract The polycycles merochlorin A and B are complex halogenated meroterpenoid natural products with significant antibacterial activities produced by the marine bacterium Streptomyces sp. strain CNH‐189. Heterologously enzymes chemical synthesis employed herein to fully reconstitute biosynthesis in vitro. interplay of a dedicated type III polyketide synthase, prenyl diphosphate an aromatic prenyltransferase allow formation highly unusual polyketide‐terpene hybrid intermediate which...
Caprazamycins are potent anti-mycobacterial liponucleoside antibiotics isolated from Streptomyces sp. MK730-62F2 and belong to the translocase I inhibitor family. Their complex structure is derived 5'-(beta-O-aminoribosyl)-glycyluridine comprises a unique N-methyldiazepanone ring. The biosynthetic gene cluster has been identified, cloned, sequenced, representing first of inhibitor. Sequence analysis revealed presence 23 open reading frames putatively involved in export, resistance,...
The vanadium-dependent chloroperoxidase Mcl24 was discovered to mediate a complex series of unprecedented transformations in the biosynthesis merochlorin meroterpenoid antibiotics. In particular, site-selective naphthol chlorination is followed by an oxidative dearomatization/terpene cyclization sequence build up stereochemically carbon framework merochlorins one step. Inspired enzyme reactivity, chemical protocol paralleling biocatalytic process developed. These studies led identification...
Abstract Cytochrome P450 monooxygenases are biocatalysts that hydroxylate or epoxidise a wide range of hydrophobic organic substrates. Their technical application is, however, limited to small number whole‐cell processes. The use the isolated enzymes is believed be impractical due their low stability, stoichiometric need expensive cofactor NAD(P)H and solubility most substrates in aqueous media. We investigated behaviour an bacterial monooxygenase (mutants CYP102A1) biphasic reaction system...
The epoxyketone proteasome inhibitors are an established class of therapeutic agents for the treatment cancer. Their unique α′,β′-epoxyketone pharmacophore allows binding to catalytic β-subunits with extraordinary specificity. Here, we report characterization first gene clusters biosynthesis natural peptidyl-epoxyketones. epoxomicin, lead compound anticancer drug Kyprolis, and eponemycin were identified in actinobacterial producer strains ATCC 53904 Streptomyces hygroscopicus 53709,...
Using automated genome analysis tools, it is often unclear to what degree genetic variability in homologous biosynthetic pathways relates structural variation. This hampers strain prioritization and compound identification can lead overinterpretation of chemical diversity. Here, we assessed the metabolic potential
Abstract Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones a unique β‐lactone building block. Herein, we present detailed investigation of their biosynthesis. Identification analysis the corresponding gene clusters indicated that both compounds assembled by rare single‐enzyme amino acid ligases. Feeding experiments with isotope‐labeled precursors in vitro biochemistry showed formation warhead is unprecedented...
Heterologous expression in well-studied model strains is a routinely applied method to investigate biosynthetic pathways. Here, we pursue comparative approach of large-scale DNA-affinity-capturing assays (DACAs) coupled with semi-quantitative mass spectrometry (MS) identify putative regulatory proteins from Streptomyces coelicolor M512, which bind the heterologously expressed gene clusters (BGCs) liponucleoside antibiotics caprazamycin and liposidomycin. Both share an almost identical...
En route: The liposidomycin biosynthetic gene cluster has been identified, cloned and heterologously expressed. A comparison with the of structurally related caprazamycins supports proposed pathway to liponucleoside formation led identification new sulfated caprazamycin derivatives. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted by authors. Please note:...
Abstract Napsamycins are potent inhibitors of bacterial translocase I, an essential enzyme in peptidoglycan biosynthesis, and classified as uridylpeptide antibiotics. They comprise N ‐methyl diaminobutyric acid, ureido group, a methionine two non‐proteinogenic aromatic amino acid residues peptide backbone that is linked to 5′‐amino‐3′‐deoxyuridine by unusual enamide bond. The napsamycin gene cluster was identified Streptomyces sp. DSM5940 using PCR probes from putative biosynthetic found S....
Abstract Metalloproteinase inhibitors often feature hydroxamate moieties to facilitate the chelation of metal ions in catalytic center target enzymes. Actinonin and matlystatins are potent metalloproteinase that comprise rare N -hydroxy-2-pentyl-succinamic acid warheads. Here we report identification characterization their biosynthetic pathways. By gene cluster comparison a combination precursor feeding studies, heterologous pathway expression deletion experiments able show...
Abstract The vanadium‐dependent chloroperoxidase Mcl24 was discovered to mediate a complex series of unprecedented transformations in the biosynthesis merochlorin meroterpenoid antibiotics. In particular, site‐selective naphthol chlorination is followed by an oxidative dearomatization/terpene cyclization sequence build up stereochemically carbon framework merochlorins one step. Inspired enzyme reactivity, chemical protocol paralleling biocatalytic process developed. These studies led...
Belactosin A, a β-lactone proteasome inhibitor, contains unique 3-(trans-2′-aminocyclopropyl)alanine moiety. We recently identified the biosynthetic gene cluster of belactosin series from Streptomyces sp. UCK14. To shed light on formation aminocyclopropylalanine, we established heterologous pathway expression, constructed set deletion mutants, and performed feeding studies for chemical complementation that include incorporation stable isotope-labeled precursors. thereby show that, in...
Abstract The biosynthetic gene clusters of the aminocoumarin antibiotics clorobiocin and coumermycin A 1 liponucleoside antibiotic caprazamycin were stably integrated into genomes different host strains derived from Streptomyces coelicolor A3(2). For heterologous expression derivatives in a chemically defined medium, inclusion 0.6% siloxylated ethylene oxide/propylene oxide copolymer Q2‐5247 growth medium proved to result 4.8‐fold increase productivity. Presumably, this acts as an oxygen...
Sulfotransferases are involved in a variety of physiological processes and typically use 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor substrate. In contrast, microbial arylsulfate sulfotransferases (ASSTs) PAPS-independent utilize arylsulfates donors. Yet, their genuine acceptor substrates unknown. this study we demonstrate that Cpz4 from Streptomyces sp. MK730-62F2 is an ASST-type sulfotransferase responsible for formation sulfated liponucleoside antibiotics. Gene...
Abstract The polycycles merochlorin A and B are complex halogenated meroterpenoid natural products with significant antibacterial activities produced by the marine bacterium Streptomyces sp. strain CNH‐189. Heterologously enzymes chemical synthesis employed herein to fully reconstitute biosynthesis in vitro. interplay of a dedicated type III polyketide synthase, prenyl diphosphate an aromatic prenyltransferase allow formation highly unusual polyketide‐terpene hybrid intermediate which...