Isolation of metabolites from the fungus Fusarium guttiforme under different culture conditions and inhibitory evaluation of proteases

• Grant number: 23/01144-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: March 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Paulo Cézar Vieira
• Grantee: Felipe Santos Furlaneto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Fungi constitute a diverse and widely spread kingdom in all regions of the biosphere, implying that, in the course of evolution, adaptation mechanisms in the face of adverse situations have become necessary. Today it is known that such microorganisms, especially filamentous fungi, have a series of genes that are grouped differently from the genes that encode molecules essential to the life of the organism: such a group of genes, called Biosynthetic Gene Clusters (BGCs), are generally inactive under ordinary conditions, such as in vitro cultivation done under laboratory conditions.Proteases present in plants are part of their defense system against invading microorganisms. Thus, it is expected that endophytic and phytopathogenic microorganisms have inhibition mechanisms of this enzymatic system developed during evolution. The search for protease inhibitors is important not only for controlling pests in agriculture, but also for prospecting new drug candidates, since proteases are prominent pharmacological targets for highly relevant diseases, such as neurodegenerative diseases, COVID-19 or Zika.This project seeks to apply the epigenetic modulation strategy included in the methodological approach known as One strain many compounds (OSMAC), which consists of using a single strain of microorganism, but using variations in growth conditions, in order to access routes that lead to the activation of silenced genes with the use of epigenetic modulators and pH variation of the culture medium in which they grow. With this, it is expected to evaluate the profiles of secondary metabolites generated and compare them to the profile obtained by traditional cultivation.After obtaining the extracts with and without epigenetic modulation produced by the fungus, the evaluation of the protease inhibition activity of these extracts will be carried out: those that present more potent activity will be submitted to chromatographic methods of separation and purification of their components and, subsequently, to structural elucidation methods, in order to be able to isolate and identify new enzymatic inhibitors.