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Metabolic induction guided by genomic-mining strategies in Burkholderia thailandensis for the biosynthesis of antibiotic-like natural products

Grant number: 16/19269-8
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Start date: February 01, 2017
End date: April 03, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:João Henrique Ghilardi Lago
Grantee:Joao Luiz Baldim Zanin
Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Microorganisms participate in biological processes as long before man discover the possibilities for its systematic use. The production of compounds with pharmacological importance from these microscopic beings is well studied since the discovery of Penicillin. Currently, genomic analyzes have provided numerous new Natural Products from microorganisms. Therefore, this work aims to analyzing Burkholderia genomes using specific algorithms to create profiles, such as, antibiotic resistance profiles. These profiles will provide candidates for metabolic induction in a model micro-organism of the genus Burkholderia, the species B. thailandensis. Microorganisms of the class ²-Proteobacteria are emerging as sources of compounds of industrial and/or pharmacological interest where most of these Natural Products were discovered from genomic analyzes. A classic example is the discovery of teixobactin through genomic studies in Eleftheria terrae, a ²-Proteobacteria representative. In this project, bioinformatics analyzes will guide the culture media composition for carbon- and nitrogen-sources using platforms for metabolism prediction, for example, KEGG platform. The metabolic inducer concentration and the recognition of promising metabolic profiles will be determined by comparison with the standard culture media optical density (with no compounds from genomic analysis) via GC-MS, HPLC and dereplication. The discovery of new compounds will be bioguided by activities from extracts and partitions against pathogenic micro-organisms by crossing all results in dynamic networks. It is believed that rational and modern strategies, as taken in this project, can create strategies to avoid spending financial resources and save time discovering new Natural Products that could act as antibiotic agents. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BALDIM, JOAO LUIZ; DA SILVA, BRUNA LIDIANE; CHAGAS-PAULA, DANIELA APARECIDA; LAGO, JOAO HENRIQUE G.; SOARES, MARISI G.. A strategy for the identification of patterns in the biosynthesis of nonribosomal peptides by Betaproteobacteria species. SCIENTIFIC REPORTS, v. 7, . (16/19269-8)
SILVA, ROBSON E.; BALDIM, JOAO L.; CHAGAS-PAULA, DANIELA A.; SOARES, MARISI G.; LAGO, JOAO H. G.; GONCALVES, V, REGGIANI; NOVAES, ROMULO D.. Predictive metabolomic signatures of end-stage renal disease: A multivariate analysis of population-based data. Biochimie, v. 152, p. 14-30, . (16/19269-8)
OLIVEIRA, EMERSON A.; MARTINS, EUDER G. A.; SOARES, MARISI G.; CHAGAS-PAULA, DANIELA A.; PASSERO, LUIZ F. D.; SARTORELLI, PATRICIA; BALDIM, JOAO L.; LAGO, JOAO HENRIQUE G.. A Comparative Study on Chemical Composition, Antileishmanial and Cytotoxic Activities of the Essential Oils from Leaves of Guarea macrophylla (Meliaceae) from Two Different Regions of São Paulo State, Brazil, Using Multivariate Statistical Analysis. Journal of the Brazilian Chemical Society, v. 30, n. 7, p. 1395-1405, . (16/00468-0, 18/07885-1, 16/19269-8)
DE SOUSA, FERNANDA S.; BALDIM, JOAO L.; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; PIEPER, PAULINE; SEAR, CLAIRE E.; ANDERSON, EDWARD A.; LAGO, JOAO HENRIQUE G.. Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design. Bioorganic & Medicinal Chemistry Letters, v. 30, n. 16, . (15/11936-2, 15/04143-6, 16/19269-8, 18/07885-1)