Genomics-Driven Discovery of a Novel Glutarimide Antibiotic from Burkholderia gladioli Reveals an Unusual Polyketide Synthase Chain Release Mechanism

A gene cluster encoding a cryptic trans-acyl transferase polyketide synthase (PKS) was identified in the genomes of Burkholderia gladioli BCC0238 and BCC1622, both isolated from the lungs of cystic fibrosis patients. Bioinfomatics analyses indicated the PKS assembles a novel member of the glutarimide class of antibiotics, hitherto only isolated from Streptomyces species. Screening of a range of growth parameters led to the identification of gladiostatin, the metabolic product of the PKS. NMR spectroscopic analysis revealed that gladiostatin, which has promising activity against several human cancer cell lines and inhibits tumor cell migration, contains an unusual 2-acyl-4-hydroxy-3-methylbutenolide in addition to the glutarimide pharmacophore. An AfsA-like domain at the C-terminus of the PKS was shown to catalyze condensation of 3-ketothioesters with dihydroxyacetone phosphate, thus indicating it plays a key role in polyketide chain release and butenolide formation.     

Preparation and characterization of polymer layer systems for validation of 3D Micro X-ray fluorescence spectroscopy

For the validation of the quantification of the newly-developed method of 3D Micro X-ray fluorescence spectroscopy (3D Micro-XRF) samples with a low average Z matrix and minor high Z elements are best suited. In a light matrix the interferences by matrix effects are minimized so that organic polymers are appropriate as basis for analytes which are more easily detected by X-ray fluorescence spectroscopy.     

Design,Synthesis and Antiparasitic Evaluation of Click Phospholipids

A library of seventeen novel ether phospholipid analogues, containing 5-membered heterocyclic rings (1,2,3-triazolyl, isoxazolyl, 1,3,4-oxadiazolyl and 1,2,4-oxadiazolyl) in the lipid portion were designed and synthesized aiming to identify optimised miltefosine analogues. The compounds were evaluated for their in vitro antiparasitic activity against Leishmania infantum and Leishmania donovani intracellular amastigotes, against Trypanosoma brucei brucei and against different developmental stages of Trypanosoma cruzi. The nature of the substituents of the heterocyclic ring (tail) and the oligomethylene spacer between the head group and the heterocyclic ring was found to affect the activity and toxicity of these compounds leading to a significantly improved understanding of their structure–activity relationships. The early ADMET profile of the new derivatives did not reveal major liabilities for the potent compounds. The 1,2,3-triazole derivative 27 substituted by a decyl tail, an undecyl spacer and a choline head group exhibited broad spectrum antiparasitic activity. It possessed low micromolar activity against the intracellular amastigotes of two L. infantum strains and T. cruzi Y strain epimastigotes, intracellular amastigotes and trypomastigotes, while its cytotoxicity concentration (CC₅₀) against THP-1 macrophages ranged between 50 and 100 μM. Altogether, our work paves the way for the development of improved ether phospholipid derivatives to control neglected tropical diseases.     

Determination of antimicrobial activity and resistance to oxidation of moringa peregrina seed oil

The antimicrobial activity of the oil extracted with n-hexane from the seeds of Moringa peregrina was tested against Staphylococcus aureus, S. epidermidis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Candida albicans, C. tropicalis and C. glabrata. The oil proved effective against all of the tested microorganisms. Standard antibiotics (netilmycin, 5-flucytocine, intraconazole and 7-amino-4-methylcoumarin-3-acetic acid) were used for comparison. The resistance to oxidation of the extracted seed oil was also determined.     

Chemical Constituents from Croton insularis

Three new clerodane‐type terpenoids, furocrotinsulolide A ( 1 ), furocrotinsulolide B ( 2 ), and crotinsulactone ( 3 ), as well as a new phenolic disaccharide ( 4 ) have been isolated from the aerial parts of Croton insularis, together with eight known compounds. Their structures were established by in‐depth 1D‐ and 2D‐NMR spectroscopy, mass spectroscopy, and quantum‐mechanical calculations.     

Konstanz summer school 2018 on isotope ecology

Abstract

Biodegradation of polychlorinated biphenyls (PCBs) in soil is considered to be very complex due to various physico-chemical factors involved. Isotope labelling technique is the best to trace fate of the xenobiotic in the environment. In this work, the uniformly ¹⁴C-labelled PCB congener 11 (3,3′-chlorobiphenyl) was chosen as a low chlorinated coplanar biphenyl which was assumed to be readily degraded by microorganisms. Pleurotus ostreatus and two Pseudomonas species, representing white rot fungi and soil bacteria were used separately or in a consortium. The amount of liberated ¹⁴CO₂ and radio-HPLC, HPLC, GC-MS, and radio-TLC analyses of extracts at the end of a two-month experiment showed that the mineralization of PCB 11 was < 0.4%, volatilization < 3.1%, and 30% of radioactivity was irreversibly bound to the soil matrix. The respective contents of all intermediate metabolites were 4.7 to 10.5 and 2.5 to 2.7% where Pseudomonas alcaligenes alone or in combination with P. putida was applied. 3-Chlorobenzoic acid was the major biodegradation product.