OSMAC approach applied to the modulation of the biosynthesis of antimicrobials by Pseudonocardia ICBG1860, an attine ant symbiont

• Grant number: 24/21508-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Mônica Tallarico Pupo
• Grantee: Guilherme José Brustello Vizin
• 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

Abstract

Natural products, or secondary metabolites, play a pivotal role in the development of biologically active compounds and are essential for discovering new drugs with antimicrobial, anticancer, and antiparasitic activities. Microorganisms, which comprise a substantial portion of global biodiversity, are rich sources of secondary metabolites due to their complex symbiotic interactions with other organisms. A notable example is the symbiosis between ants of the Attini tribe and actinobacteria of the genus Pseudonocardia, which produce antimicrobial compounds to protect the fungus cultivated by the ants against fungal pathogens such as Escovopsis.Studies of these bacteria have revealed new compounds, including dentigerumycin, gerumycins A-C, selvamicin, and pseudonocardones A-C, many of which exhibit antimicrobial activity against human pathogens. Recently, the Microorganism Chemistry Laboratory at FCFRP-USP identified attinimycin, a compound with antifungal activity against Escovopsis and Candida albicans, which is exclusively present in Pseudonocardia strains associated with attine ants in Brazil.The discovery of new bioactive molecules faces challenges due to traditional screening methods. To address this, modern metabolomics tools, such as sequential mass spectrometry (MS/MS) and the GNPS platform, facilitate dereplication and identification of new metabolites. Another promising strategy is the OSMAC (One Strain Many Compounds) approach, which diversifies metabolite production by manipulating culture parameters, thereby unlocking greater chemical diversity.This project aims to apply the OSMAC approach to the Pseudonocardia sp. strain ICBG 1860, hypothesizing that this technique can elicit the production of minor and novel compounds with antimicrobial activity, significantly contributing to the discovery of new bioactive natural products.