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A multi-omics reciprocal analysis for characterization of bacterial metabolism

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Arini, Gabriel Santos ; Borelli, Tiago Cabral ; Ferreira, Elthon Gois ; de Felicio, Rafael ; Rezende-Teixeira, Paula ; Pedrino, Matheus ; Rabico, Franciene ; de Siqueira, Guilherme Marcelino Viana ; Mencucini, Luiz Gabriel ; Tsuji, Henrique ; Andrade, Lucas Sousa Neves ; Garrido, Leandro Maza ; Padilla, Gabriel ; Gil-de-la-Fuente, Alberto ; Wang, Mingxun ; Lopes, Norberto Peporine ; Trivella, Daniela Barretto Barbosa ; Costa-Lotufo, Leticia Veras ; Guazzaroni, Maria-Eugenia ; da Silva, Ricardo Roberto
Total Authors: 20
Document type: Journal article
Source: FRONTIERS IN MOLECULAR BIOSCIENCES; v. 12, p. 15-pg., 2025-03-20.
Abstract

Introduction Exploiting microbial natural products is a key pursuit of the bioactive compound discovery field. Recent advances in modern analytical techniques have increased the volume of microbial genomes and their encoded biosynthetic products measured by mass spectrometry-based metabolomics. However, connecting multi-omics data to uncover metabolic processes of interest is still challenging. This results in a large portion of genes and metabolites remaining unannotated. Further exacerbating the annotation challenge, databases and tools for annotation and omics integration are scattered, requiring complex computations to annotate and integrate omics datasets.Methods Here we performed a two-way integrative analysis combining genomics and metabolomics data to describe a new approach to characterize the marine bacterial isolate BRA006 and to explore its biosynthetic gene cluster (BGC) content as well as the bioactive compounds detected by metabolomics.Results and Discussion We described BRA006 genomic content and structure by comparing Illumina and Oxford Nanopore MinION sequencing approaches. Digital DNA:DNA hybridization (dDDH) taxonomically assigned BRA006 as a potential new species of the Micromonospora genus. Starting from LC-ESI(+)-HRMS/MS data, and mapping the annotated enzymes and metabolites belonging to the same pathways, our integrative analysis allowed us to correlate the compound Brevianamide F to a new BGC, previously assigned to other function. (AU)

FAPESP's process: 20/02207-5 - Inventorying secondary metabolism applying metabolomic strategies: contribution to the Brazilian biodiversity valuation
Grantee:Norberto Peporine Lopes
Support Opportunities: BIOTA-FAPESP Program - Thematic Grants
FAPESP's process: 21/09375-3 - Development of new microbial platforms tolerant to lignocellulosic biomass hydrolysates
Grantee:Matheus Pedrino Gonçalves
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 19/25432-7 - Searching for new molecular tools to enhance Pseudomonas putida robustness to abiotic stresses
Grantee:Guilherme Marcelino Viana de Siqueira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 21/08235-3 - Unraveling the evolutionary logic and structure of the marine resistome: a deep structured learning approach to discovery of evolutionary constraints
Grantee:Tiago Cabral Borelli
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 21/01748-5 - Discovery and development of new non-model bacterial chassis for biotechnological applications
Grantee:María Eugenia Guazzaroni
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 17/18922-2 - Development of a computing platform extensible and modular for metabolomics and metagenomics analysis: innovation with the discovery of new enzymatic activities and natural products of pharmaceutical interest derived
Grantee:Ricardo Roberto da Silva
Support Opportunities: BIOTA-FAPESP Program - Young Investigators Grants
FAPESP's process: 21/10401-9 - Detection and repository optimization of fragmentation spectra from biological signals in metabolomics studies
Grantee:Gabriel Santos Arini
Support Opportunities: Scholarships in Brazil - Doctorate