Access to fungal chemodiversity: isolation of inhibitors of cysteine proteases

• Grant number: 23/00874-2
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2023
• End date: December 23, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Paulo Cézar Vieira
• Grantee: Victoria Perini Pederiva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery, AP.CEPID
• Associated scholarship(s): 23/16158-4 - Metabolomics approach to access fungal chemodiversity through co-cultivation, BE.EP.MS

Abstract

Proteases are biological macromolecules responsible for protein degradation and their imbalance is related to several pathologies. Fruits such as papaya and pineapple have a high content of proteases, most of which are papain-like cysteine proteases, which participate in the plant's defense system against pathogens.However, some fungi can infect them, suggesting that they produce protease inhibitors. In this context, this work intends to investigate microorganisms that infect these fruits through their isolation and cultivation in the laboratory in different cultivation media and co-cultivation to access silent biosynthetic pathways and obtain new bioactive metabolites from these interactions. Thus, it is possible to access and expand the chemodiversity of these microorganisms due to the activation of these biosynthetic pathways that lead to new natural products that would not be produced in axenic lineages. It is noteworthy that parasites that cause malaria and Chagas disease also have cysteine proteases essential for parasite survival and pathogenicity. Thus, the enzymatic inhibition of cysteine proteases can lead to the development of products of interest to the pharmaceutical sector.The fungi to be studied first are Fusarium guttiforme and Fusarium proliferatum, both pineapple invaders. The extracts with promising bioactivities will be tested for inhibition of cysteine proteases, initially in papain, but it is also of interest to the laboratory to study the inhibitory potential in cruzain, falcipain and human cathepsins. For the identification of metabolites spectroscopic and spectrometric techniques will be used and the enzymatic assays to determine the inhibitory potential will be monitored by spectrophotometry and/or fluorimetry.