A5014195354- Microbial Natural Products and Biosynthesis
- Bacteriophages and microbial interactions
- Genomics and Phylogenetic Studies
- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Use and Resistance
- Click Chemistry and Applications
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Antibiotic Resistance in Bacteria
- Marine Sponges and Natural Products
- Chemical Synthesis and Analysis
- Biochemical and Molecular Research
- Synthetic Organic Chemistry Methods
- Parasites and Host Interactions
- Reproductive tract infections research
- Antimicrobial Peptides and Activities
- Synthesis and Characterization of Heterocyclic Compounds
- Traditional and Medicinal Uses of Annonaceae
- Actinomycetales infections and treatment
- Bacterial Identification and Susceptibility Testing
- Fungal Biology and Applications
- Helminth infection and control
- Probiotics and Fermented Foods
- Neonatal and Maternal Infections
- Cancer therapeutics and mechanisms
Norwich Research Park
2015-2023
John Innes Centre
2013-2023
German Center for Infection Research
2021-2022
Norwich University
2016
University of Tübingen
2006-2011
ObjectivesAminocoumarin antibiotics are potent inhibitors of bacterial DNA gyrase. We investigated the inhibitory and antibacterial activity naturally occurring aminocoumarin six structural analogues (novclobiocins) against gyrase topoisomerase IV from Escherichia coli Staphylococcus aureus as well effect potassium sodium glutamate on these enzymes.
Abstract Erythromycin, avermectin and rapamycin are clinically useful polyketide natural products produced on modular synthase multienzymes by an assembly-line process in which each module of enzymes turn specifies attachment a particular chemical unit. Although encoding genes have been successfully engineered to produce novel analogues, the can be relatively slow, inefficient, frequently low-yielding. We now describe method for rapidly recombining gene clusters replace, add or remove...
We report the identification of biosynthetic gene cluster for unusual antibiotic anthracimycin (atc) from marine derived producer strain Streptomyces sp. T676 isolated off St. John's Island, Singapore. The 53 253 bps atc locus includes a trans-acyltransferase (trans-AT) polyketide synthase (PKS), and heterologous expression in coelicolor resulted production. Analysis revealed that is likely generated by four PKS products AtcC–AtcF without involvement post-PKS tailoring enzymes, pathway...
A growing number of natural products appear to arise from biosynthetic pathways that involve pericyclic reactions. We show here for the heronamides this can occur via two spontaneous involving alternative thermal or photochemical intramolecular cycloadditions.
We report the genome sequence of Planobispora rosea ATCC 53733, a mycelium-forming soil-dweller belonging to one lesser studied genera Actinobacteria and producing thiopeptide GE2270. The P. presents considerable convergence in gene organization function with other members family Streptosporangiaceae, significant number (44%) shared orthologs. Patterns expression cultures during exponential stationary phase have been analyzed using whole transcriptome shotgun sequencing by proteome analysis....
Glycopeptide antibiotics are used to treat severe multidrug resistant infections caused by Gram-positive bacteria. Dalbavancin is a second generation glycopeptide approved for human use, which obtained from A40926, lipoglycopeptide produced Nonomuraea sp. ATCC39727 as mixture of biologically active congeners mainly differing in the fatty acid chains present on glucuronic moiety. In this study, we constructed double mutant A40926 producer strain lacking dbv23, and thus defective mannose...
To meet the ever-growing demands of antibiotic discovery, new chemical matter and targets are urgently needed. Many potent natural product antibiotics which were previously discarded can also provide lead molecules drug targets. One such example is structurally unique β-lactone obafluorin, produced by Pseudomonas fluorescens ATCC 39502. Obafluorin active against both Gram-positive -negative pathogens; however, biological target was unknown. We now report that obafluorin threonyl-tRNA...
Complex formation with ferric iron protects the β-lactone moiety of obafluorin from hydrolysis and potentiates antibiotic activity.
Gonorrhea remains a major global public health problem because of the high incidence infection (estimated 82 million cases in 2020) and emergence spread Neisseria gonorrhoeae strains resistant to previous current antibiotics used treat infections. Given dearth new that are likely enter clinical practice near future, there is concern untreatable gonorrhea might emerge. In response this crisis, World Health Organization (WHO), partnership with Global Antibiotic Research Development Partnership...
Corallopyronin A (CorA), a natural product antibiotic of Corallococcus coralloides , inhibits the bacterial DNA-dependent RNA polymerase. It is active against essential Wolbachia endobacteria filarial nematodes, preventing development, causing sterility and killing adult worms. CorA being developed to treat neglected tropical diseases onchocerciasis lymphatic filariasis caused by -containing filariae. For this, we have completed standard Absorption, Distribution, Metabolism, Excretion...
In vivo studies in mice provide a valuable model to test novel active pharmaceutical ingredients due their low material need and the fact that are frequently used as species for early efficacy models. However, preclinical vitro evaluations of formulation principles still lacking. The development silico models supported evaluation anti-infective corallopyronin A (CorA). To this end, CorA solubility-enhanced amorphous solid dispersion formulations, comprising povidone or copovidone, were...
Abstract To meet the ever-growing demand of antibiotic discovery, new chemical matter and targets are urgently needed. Many potent natural product antibiotics which were previously discarded can also provide lead molecules drug targets. One such example is structurally unique β -lactone obafluorin, produced by Pseudomonas fluorescens ATCC 39502. Obafluorin active against both Grampositive -negative pathogens, however biological target was unknown. We now report that obafluorin...