Search Results (3)

Ochratoxin A is historically the most notable secondary metabolite of Aspergillus ochraceus on account of its toxicity to animals and fish. Currently, over 150 compounds of diverse structure and biosynthesis is a challenge to predict the array for any particular isolate. A brief focus 30 years ago on the failure to produce ochratoxins in foods in Europe and the USA revealed consistent failures to produce ochratoxin A by isolates from some USA beans. Analysis for familiar or novel metabolites particularly focused on a compound for which mass and NMR analyses were inconclusive. Resort to ¹⁴C-labelled biosynthetic precursors, particularly phenylalanine, to search for any close alternative to ochratoxins, was combined with conventional shredded-wheat/shaken-flask fermentation. This yielded, for an extract, an autoradiograph of a preparative silica gel chromatogram, which was subsequently analysed for an excised fraction using spectroscopic methodologies. Circumstances then delayed progress for many years until the present collaboration revealed notoamide R. Meanwhile, pharmaceutical discovery around the turn of the millennium revealed stephacidins and notoamides, biosynthetically combining indole, isoprenyl and diketopiperazine components. Later, in Japan, notoamide R was added as a metabolite of an Aspergillus sp. isolated from a marine mussel, and the compound was recovered from 1800 Petri dish fermentations. Renewed attention to our former studies in England has since shown for the first time that notoamide R can be a prominent metabolite of A. ochraceus, sourced from a single shredded wheat flask culture with its structure confirmed by spectroscopic data, and in the absence of ochratoxins. Renewed attention to the archived autoradiographed chromatogram allowed further exploration, but in particular has stimulated a fundamental biosynthetic approach to considering influences redirecting intermediary metabolism to secondary metabolite accumulation. Full article

In nature, secondary metabolites have been proven to be the essential communication media between co-occurring microorganisms and to influence their relationship with each other. In this study, we conducted a metabolomics survey of the secondary metabolites of an artificial co-culture related to a hydrothermal vent fungal–bacterial community comprising Aspergillus sclerotiorum and Streptomyces and their reciprocal relationship. The fungal strain was found to increase the secretion of notoamides and the compound cyclo(Pro-Trp) produced by the actinomycetes strain was discovered to be the responsible molecule. This led to the hypothesis that the fungi transformed cyclo(Pro-Trp) synthesized by the actinomycetes as the biosynthetic precursors of notoamides in the chemical communication. Further analysis showed Streptomyces sp. WU20 was efficient in transforming amino acids into cyclo(Pro-Trp) and adding tryptophan as well as proline into the chemical communication enhanced the induction of the notoamide accumulation. Thus, we propose that the microbial transformation during the synthetic metabolically-mediated chemical communication might be a promising means of speeding up the discovery of novel bioactive molecules. The objective of this research was to clarify the mechanism of microbial transformation for the chemical communication. Besides, this research also highlights the utility of mass spectrometry-based metabolomics as an effective tool in the direct biochemical analysis of community metabolites. Full article

The investigation of marine natural products (MNPs) as key resources for the discovery of drugs to mitigate the COVID-19 pandemic is a developing field. In this work, computer-aided drug design (CADD) approaches comprising ligand- and structure-based methods were explored for predicting SARS-CoV-2 main protease (M^pro) inhibitors. The CADD ligand-based method used a quantitative structure–activity relationship (QSAR) classification model that was built using 5276 organic molecules extracted from the ChEMBL database with SARS-CoV-2 screening data. The best model achieved an overall predictive accuracy of up to 67% for an external and internal validation using test and training sets. Moreover, based on the best QSAR model, a virtual screening campaign was carried out using 11,162 MNPs retrieved from the Reaxys^® database, 7 in-house MNPs obtained from marine-derived actinomycetes by the team, and 14 MNPs that are currently in the clinical pipeline. All the MNPs from the virtual screening libraries that were predicted as belonging to class A were selected for the CADD structure-based method. In the CADD structure-based approach, the 494 MNPs selected by the QSAR approach were screened by molecular docking against M^pro enzyme. A list of virtual screening hits comprising fifteen MNPs was assented by establishing several limits in this CADD approach, and five MNPs were proposed as the most promising marine drug-like leads as SARS-CoV-2 M^pro inhibitors, a benzo[f]pyrano[4,3-b]chromene, notoamide I, emindole SB beta-mannoside, and two bromoindole derivatives. Full article