14 research outputs found
Activated zeolite - Suitable carriers for microorganisms in anaerobic digestion processes?
Peptidomimetic antibiotics target outer membrane biogenesis in Pseudomonas aeruginosa
Antibiotics with new mechanisms of action are urgently required to combat the growing health
threat posed by resistant pathogenic microorganisms. We synthesized a family of peptidomimetic
antibiotics, based on the antimicrobial peptide protegrin I. Several rounds of optimization gave a
lead compound that was active in the nanomolar range against gram-negative Pseudomonas sp.,
but was largely inactive against other Gram-negative and Gram-positive bacteria. Biochemical
and genetic studies showed the peptidomimetics had a non-membrane-lytic mechanism of action
and identified a homologue of the ß-barrel protein LptD (Imp/OstA), which functions in outer
membrane biogenesis, as a cellular target. The peptidomimetic showed potent antimicrobial
activity in a mouse septicemia infection model. Drug-resistant strains of Pseudomonas are a
serious health problem, so this family of antibiotics may have important therapeutic applications
State Governance Beyond the ‘Shadow of Hierarchy’: A social mechanisms perspective on governmental CSR policies
Cytotoxic Angucycline Class Glycosides from the Deep Sea Actinomycete Streptomyces lusitanus
A thermodynamic evaluation of antibody-surface interactions in multimodal cation exchange chromatography
Biomimetic Synthesis and Proposal of Relative and Absolute Stereochemistry of Heronapyrrole C
Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis
Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis