Mining cyanobacterial genomes for secondary metabolite biosynthetic gene clusters

• Grant number: 21/14754-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2022
• End date: February 29, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Camila Manoel Crnkovic
• Grantee: João Pedro Brandão Domingues
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Secondary metabolites represent an important source of molecules that inspire the discovery and development of pharmaceutical drugs. Yet, natural product discovery is a challenging process. Expanding source diversity and improving bioprospection approaches are critical to enhancing the identification of novel molecules. Cyanobacteria encompass a diverse phylum of microorganisms known to produce secondary metabolites with pharmaceutical and biotechnological applications. Secondary metabolites from Brazilian cyanobacteria remain largely underexplored, representing a promising source of chemical scaffolds. As genome sequencing becomes more accessible and bioinformatics develops, the genome mining pipeline gains a significant role in natural products research. This project aims at investigating cyanobacterial genome sequences by genome mining to identify and prioritize biosynthetic gene clusters (BGCs) for natural product discovery. Our first aim is to mine genome sequences from cyanobacteria collected in Brazil that are publicly available on GenBank. The quality of the genomes assemblies will be assessed using QUAST, followed by genome mining using antiSMASH. A systematic rationale will be developed for prioritizing BGCs for natural product discovery, based on previously studied cyanobacterial genomes that were shown to harbor BGCs encoding for diverse secondary metabolites. The rationale will be applied to the analysis of genomes of Brazilian cyanobacteria. Results will provide us with a landscape of the distribution of secondary metabolite BGCs in Brazilian cyanobacteria, as well as a list of promising BGCs. Our second aim is to sequence and mine two new cyanobacterial genomes isolated from Brazilian strains as part of our bioprospecting efforts. (AU)