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Metabolomic and genomic study of fungi aiming at obtaining bioactive substances


The present project intends to advance the frontier of knowledge between metabolomics and genomics in order to search for secondary metabolites with antitumor potential from endophytic fungi and basidiomycetes. Thus, it is proposed to perform the dereplication of extracts obtained from basidiomycete fungi as well as extracts obtained from the fermentation of endophytic fungi associated with selected plant species. The de-replication of the components present in the extracts will be performed by a hyphenated LC-HRMS-MS technique and aided by the open platform Global Natural Products Social Molecular Networking (GNPS) as a tool for annotation/identification of substances, associated with the tests to evaluate the antitumor potential of the extracts. Additionally, we intend to perform the genomic analysis of the selected fungi through genome sequencing, annotation of the cluster of biosynthetic genes (BGC), suggested as responsible to produce metabolites that prove to be promising in the metabolomic/biological study, and heterologous expression in a model organism for the production of the antitumor metabolite on a large scale. In extracts in which possibly unpublished substances are detected, evaluated through molecular networks, or that are active against models of antitumor activity, they will be subjected to chromatographic fractionation so that the secondary metabolites responsible for the activity are purified and their structures determined by spectroscopic techniques and spectrometric. Finally, after the identification of the active substances, they can be submitted to tests to evaluate the antiproliferative activity and to determine the production of nitric oxide to define the antitumor mode of action. The project will also have a team of researchers with expertise in the chemistry of natural products and collaborators with knowledge in molecular biology and biological assays. (AU)

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