Production of Polypeptin A analogues by Paenibacillus elgii strain AC13 and quorum sensing dependent bacterial processes

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Ortega, Daniel Barros lattes
Orientador(a): Barreto, Cristine Chaves lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Católica de Brasília
Programa de Pós-Graduação: Programa Stricto Sensu em Ciências Genômicas e Biotecnologia
Departamento: Escola de Saúde e Medicina
País: Brasil
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Palavras-chave em Inglês:
Área do conhecimento CNPq:
Resumo em Inglês: Quorum sensing (QS) are sophisticated communication networks based on metabolic exchanges that influence bacteria processes such as reproduction, sporulation, biofilm formation, virulence and antimicrobials expression. Non-ribosomal peptides (NRP) use non-proteinogenic amino acids as building blocks, which increase the number of possible templates when compared to standard ribosomal synthesis process. Naturally produced by Paenibacillus elgii, the NRP family of Pelgipeptins (PGP) consists of five cyclic and cationic lipopeptides comprising nine amino acids and a fatty acid chain. Linearization of NRP similar to PGPs have improved antifungal activity against pathogenic Candida albicans. Paenibacillus elgii strain AC13 was isolated from soil samples of the Brazilian Cerrado. PGPs produced by AC13 were active against Escherichia coli, Staphylococcus aureus and multidrug resistant Klebsiella pneumoniae. Strain AC13 also synthesizes linear counterparts or PGPs in nutrient broth. Growth parameters, PGPs quantification, and partial characterization of produced lipopeptides suggest that strain AC13 is able to modulate its lipopeptides production based on variations of its environment or initial population. Molecular networking analysis indicates that the precursor mass of 1,101.7052 Da (PGP-B) is connected to the gene leuB pathway, responsible to code 3-isopropylmalate dehydrogenase described for P. dendritiformis C454, P. selenitireducens, P. yonginensis and P. amylolyticus. The enzyme is part of leucine biosynthetic pathway and is responsible to catalyze the oxidation of 3-isopropylmalate. Molecular networking analysis also indicates that the enzyme responsible to synthesize O-acetyl-L-homoserine (gene metAA) expressed by Lysinibacillus sp. strain FJAT-14222 is connected to precursor mass 416.7368 Da. Among QS signaling pathways, N-acyl-homoserine lactones occur as signaling molecules for more than 70 different species of diderm bacteria. QS communication can be interrupted by reducing the activity of signaling receptor proteins, their synthesis or by synthetic molecules analogous to QS signaling compounds, increasing the strategies on fighting against multidrug resistant microorganisms. Notwithstanding, a better understanding of the overlap between system biology and advanced molecular network techniques is needed.
Link de acesso: https://bdtd.ucb.br:8443/jspui/handle/tede/2603
Resumo: Quorum sensing (QS) are sophisticated communication networks based on metabolic exchanges that influence bacteria processes such as reproduction, sporulation, biofilm formation, virulence and antimicrobials expression. Non-ribosomal peptides (NRP) use non-proteinogenic amino acids as building blocks, which increase the number of possible templates when compared to standard ribosomal synthesis process. Naturally produced by Paenibacillus elgii, the NRP family of Pelgipeptins (PGP) consists of five cyclic and cationic lipopeptides comprising nine amino acids and a fatty acid chain. Linearization of NRP similar to PGPs have improved antifungal activity against pathogenic Candida albicans. Paenibacillus elgii strain AC13 was isolated from soil samples of the Brazilian Cerrado. PGPs produced by AC13 were active against Escherichia coli, Staphylococcus aureus and multidrug resistant Klebsiella pneumoniae. Strain AC13 also synthesizes linear counterparts or PGPs in nutrient broth. Growth parameters, PGPs quantification, and partial characterization of produced lipopeptides suggest that strain AC13 is able to modulate its lipopeptides production based on variations of its environment or initial population. Molecular networking analysis indicates that the precursor mass of 1,101.7052 Da (PGP-B) is connected to the gene leuB pathway, responsible to code 3-isopropylmalate dehydrogenase described for P. dendritiformis C454, P. selenitireducens, P. yonginensis and P. amylolyticus. The enzyme is part of leucine biosynthetic pathway and is responsible to catalyze the oxidation of 3-isopropylmalate. Molecular networking analysis also indicates that the enzyme responsible to synthesize O-acetyl-L-homoserine (gene metAA) expressed by Lysinibacillus sp. strain FJAT-14222 is connected to precursor mass 416.7368 Da. Among QS signaling pathways, N-acyl-homoserine lactones occur as signaling molecules for more than 70 different species of diderm bacteria. QS communication can be interrupted by reducing the activity of signaling receptor proteins, their synthesis or by synthetic molecules analogous to QS signaling compounds, increasing the strategies on fighting against multidrug resistant microorganisms. Notwithstanding, a better understanding of the overlap between system biology and advanced molecular network techniques is needed.