Study of the association of tailoring enzymes with secondary metabolite production enzymes, and construction of predictors of products and loci biosynthetic.

• Grant number: 25/02990-5
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2025
• End date: December 31, 2029
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Robson Francisco de Souza
• Grantee: Eduardo Pereira Soares
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/10577-0 - Biology of Bacteria and Bacteriophages Research Center, AP.CEPID

Abstract

The demand for new bioactive compounds has been increasing significantly, driven by the growing need for more efficient antibiotics against super-resistant bacteria. In this context, peptide natural products are compounds with broad functional diversity that include both ribosomal peptides (RiPPs) and non-ribosomal peptides (NRPs), whose synthesis is independent of the translation machinery. Both types of peptides are used by the pharmaceutical industry, but there is still significant opportunity to expand the repertoire of peptide-based bioactive compounds, based on modifications introduced by specialized enzymes. This study aims to investigate the repertoire of modifying enzymes and their relationship with the enzymes responsible for producing these molecules, as well as their products and pathways. The investigation will initially focus on analyzing the sequences of modifying enzymes of peptide natural products, using them as anchors to identify the producing enzymes and characterize the relationships between the two sets, outlining their evolutionary histories and functional relationships. Then, we will work on discovering new compounds and classes of natural products based on the relationships identified in the first part of this study. The inference of metabolic pathways and final products will be carried out alongside efforts to refine and develop new methodologies for genomic analyses, thus contributing to advancements in the fields of bioactive compound discovery and bioinformatics.