Publications by authors named "Felix Trottmann"

Furan-functionalized peptides are of significant pharmacological interest due to their pronounced bioactivities and unique potential for orthogonal bioconjugation and derivatization. However, naturally occurring peptides with furyl side chains are exceedingly rare. This study presents a streamlined method to predict and assess the microbial production of peptides incorporating 3-furylalanine (Fua) moieties.

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l-(+)-Muscarine (1)-producing mushrooms pose a severe threat to human health as ingestion can result in circulatory collapse or even death. However, their metabolic profile is surprisingly poorly understood, including knowledge of poison release and potentially toxic congeners. In the mycelium of the 1-producing fool's funnel mushroom Clitocybe rivulosa, we identified 4'-phosphomuscarine (2) as the major natural product.

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Various nonribosomal peptide synthetases (NRPSs) create structural and functional diversity by incorporating α-hydroxy acids into peptide backbones. Trigonic acid, an unusual cyclopropanol-substituted hydroxy acid, is the source of the molecular warhead of malleicyprol, a critical virulence factor of human and animal pathogens of the Burkholderia pseudomallei (BP) group. The process of selecting and loading this building block remained enigmatic as the NRPS module designated for this task is incomplete.

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Cyclopropanol rings are highly reactive and may function as molecular "warheads" that affect natural product bioactivity. Yet, knowledge on their biosynthesis is limited. Using gene cluster analyses, isotope labeling, and in vitro enzyme assays, we shed first light on the biosynthesis of the cyclopropanol-substituted amino acid cleonine, a residue in the antimicrobial depsipeptide valgamicin C and the cytotoxic glycopeptide cleomycin A2.

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Enzymes are increasingly recognized as valuable (bio)catalysts that complement existing synthetic methods. However, the range of biotransformations used in the laboratory is limited. Here we give an overview on the biosynthesis-inspired discovery of novel biocatalysts that address various synthetic challenges.

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Psilocybe "magic mushrooms" are chemically well understood for their psychotropic tryptamines. However, the diversity of their other specialized metabolites, in particular terpenoids, has largely remained an open question. Yet, knowledge on the natural product background is critical to understand if other compounds modulate the psychotropic pharmacological effects.

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Bacterial pathogens of the (BP) group cause life-threatening infections in both humans and animals. Critical for the virulence of these often antibiotic-resistant pathogens is the polyketide hybrid metabolite malleicyprol, which features two chains, a short cyclopropanol-substituted chain and a long hydrophobic alkyl chain. The biosynthetic origin of the latter has remained unknown.

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An essential step in the biosynthesis of polyketide and non-ribosomal peptide natural products is cleavage of the thioester bond that tethers the acyl/peptidyl chain to its biosynthetic enzyme. In modular polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) chain release is typically catalysed by a single C-terminal thioesterase domain. A clear exception is the bimodular PKS-NRPS BurA that produces gonyol-an intermediate in the biosynthesis of the cytotoxic virulence factor malleicyprol.

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Nonribosomal peptide synthetases (NRPSs) are a vast source of valuable natural products, and re-engineering them is an attractive path toward structurally diversified active compounds. NRPS engineering often requires heterologous expression, which is hindered by the enormous size of NRPS proteins. Protein splitting and docking domain insertion have been proposed as a strategy to overcome this limitation.

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Bacteria of the Burkholderia pseudomallei (BP) group pose a global health threat, causing the infectious diseases melioidosis, a common cause of pneumonia and sepsis, and glanders, a contagious zoonosis. A trait of BP bacteria is a conserved gene cluster coding for the biosynthesis of polyketides (malleicyprols) with a reactive cyclopropanol unit that is critical for virulence. Enzymes building this warhead represent ideal targets for antivirulence strategies but the biochemical basis of cyclopropanol formation is unknown.

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Psilocybin (1) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin (2, 4-hydroxy-N,N-dimethyltryptamine), a potent psychedelic that exerts remarkable alteration of human consciousness. In contrast, the positional isomer bufotenin (7, 5-hydroxy-N,N-dimethyltryptamine) differs significantly in its reported pharmacology. A series of experiments was designed to explore chemical differences between 2 and 7 and specifically to test the hypothesis that the C-4 hydroxy group of 2 significantly influences the observed physical and chemical properties through pseudo-ring formation via an intramolecular hydrogen bond (IMHB).

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Pathogenic bacteria of the Burkholderia pseudomallei group cause severe infectious diseases such as glanders and melioidosis. Malleicyprols were identified as important bacterial virulence factors, yet the biosynthetic origin of their cyclopropanol warhead has remained enigmatic. By a combination of mutational analysis and metabolomics we found that sulfonium acids, dimethylsulfoniumpropionate (DMSP) and gonyol, known as osmolytes and as crucial components in the global organosulfur cycle, are key intermediates en route to the cyclopropanol unit.

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The psychotropic effects of Psilocybe "magic" mushrooms are caused by the l-tryptophan-derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l-tryptophan-derived β-carbolines as their natural products, which was confirmed by 1D and 2D NMR spectroscopy.

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Burkholderia species such as B. mallei and B. pseudomallei are bacterial pathogens causing fatal infections in humans and animals (glanders and melioidosis), yet knowledge on their virulence factors is limited.

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In microbial interactions bacteria employ diverse molecules with specific functions, such as sensing the environment, communication with other microbes or hosts, and conferring virulence. Insights into the molecular basis of bacterial communication are thus of high relevance for ecology and medicine. Targeted gene activation and in vitro studies revealed that the cell-to-cell signaling molecule and disease mediator IQS (aeruginaldehyde) of the human pathogen Pseudomonas aeruginosa and related bacteria derives from the siderophore pyochelin.

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The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the and leafcutter ants, which harvest fresh leaves to feed their fungus. and many other attines vertically transmit a mutualistic strain of and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus .

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