Identificação de assinaturas sistêmicas associadas à tolerância ao etanol em linhagens de Saccharomyces cerevisiae
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Data
2019-07-01
Autores
Wolf, Ivan Rodrigo
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A crescente demanda por combustíveis fósseis e as instabilidades econômicas relacionadas à sua utilização despertam o interesse no desenvolvimento de biocombustíveis tais como o bioetanol. O processo de produção mais comum do bioetanol é a tecnologia de primeira geração, no qual o organismo mais amplamente utilizado é a levedura Saccharomyces cerevisiae. No entanto, a alta concentração de etanol gera toxicidade para S. cerevisiae e constitui um dos fatores limitantes na produção deste bioetanol. Assim, a produção de linhagens mais resistentes a esse estressor constitui um ponto chave no desenvolvimento dos processos biotecnológicos relacionados ao bioetanol. Nesse contexto, análises sistêmicas são pouco empregadas para o entendimento do fenômeno de tolerância ao etanol, deixando a busca por genes candidatos algo bastante laborioso e custoso. Assim, as diferenças entre linhagens pouco tolerantes (LT) e altamente tolerantes (HT) ao etanol (EtOH) foram analisadas por meio de ferramentas de bioinformática como a biologia de sistemas e a análises de transcriptomas. Os resultados mostraram que as linhagens HT e LT utilizam inicialmente um sistema de resposta à estresse comum, mas que devido as mudanças na estrutura das redes metabólicas, regulatórias e de interação proteína-proteína de cada linhagem, mecanismos de resposta ao estresse por etanol distintos são ativados em cada grupo. As linhagens LT mantém a homeostase da célula com o ciclo celular ativo, efetuando o ajuste dos metabolismos ao custo de que elementos transponíveis ficam ativos e agentes anti oxidantes importantes deixam de ser produzidos, permitindo que ocorram danos no DNA. As linhagens HT interrompem seu ciclo celular e boa parte do metabolismo, porém, elas mantêm a produção e reparo de proteínas para estabilizar as membranas celulares e o controle de espécies reativas de oxigênio (ROS) em conjunto com a metabolização do etanol. Uma vez que o EtOH está sendo utilizado para obtenção de carbono no ciclo do ácido cítrico, as linhagens HT resistem a concentrações maiores de etanol. Assim, o conhecimento aqui gerado poderá ser aproveitado para enriquecer as discussões futuras sobre o fenômeno estudado e o desenvolvimento biotecnológico.
The increasing demand and economic instabilities related to the use of fossil fuels raised interest in the development of biofuels such as bioethanol. The most common bioethanol production process is from the first generation technology, in which the most widely used organism is the yeast Saccharomyces cerevisiae. However, the high concentration of ethanol generates toxicity to S. cerevisiae and this is one of the limiting factors in the bioethanol production. Thus, the production of more resistant strains to this stressor is crucial to the development of biotechnological processes related to bioethanol. The systems analyzes are poorly explored to understand the ethanol tolerance phenomenon, leading the search for candidate genes labor intensive and expensive. Thus, the differences between low tolerant (LT) and high tolerant (HT) strains to ethanol (EtOH) were analyzed using bioinformatics tools like systems biology and transcriptome analysis. The results showed that HT and LT strains initially used a common stress response system but due to changes in the network structure of metabolic, regulatory, and protein-protein interactions of each strain, different mechanisms of stress response are activated in each group. LT strains maintain the cellular homeostasis activating cell cycle, and adjusting metabolisms, despite activation of transposable elements and disruption of important anti-oxidant agents production, allowing the occurrence of DNA damage. HT strains disrupt the cell cycle and most of metabolisms, but maintaining protein production and repair to stabilize cell membranes and control reactive oxygen species (ROS), working together with the ethanol metabolism. Moreover, HTs are using the EtOH to obtain carbon in the citric acid cycle, thus, it may be the reason of HT strains surpass high ethanol concentration. Altogether, the knowledge here generated may be used to enrich future discussions about the studied phenomenon and to provide biotechnological development.
The increasing demand and economic instabilities related to the use of fossil fuels raised interest in the development of biofuels such as bioethanol. The most common bioethanol production process is from the first generation technology, in which the most widely used organism is the yeast Saccharomyces cerevisiae. However, the high concentration of ethanol generates toxicity to S. cerevisiae and this is one of the limiting factors in the bioethanol production. Thus, the production of more resistant strains to this stressor is crucial to the development of biotechnological processes related to bioethanol. The systems analyzes are poorly explored to understand the ethanol tolerance phenomenon, leading the search for candidate genes labor intensive and expensive. Thus, the differences between low tolerant (LT) and high tolerant (HT) strains to ethanol (EtOH) were analyzed using bioinformatics tools like systems biology and transcriptome analysis. The results showed that HT and LT strains initially used a common stress response system but due to changes in the network structure of metabolic, regulatory, and protein-protein interactions of each strain, different mechanisms of stress response are activated in each group. LT strains maintain the cellular homeostasis activating cell cycle, and adjusting metabolisms, despite activation of transposable elements and disruption of important anti-oxidant agents production, allowing the occurrence of DNA damage. HT strains disrupt the cell cycle and most of metabolisms, but maintaining protein production and repair to stabilize cell membranes and control reactive oxygen species (ROS), working together with the ethanol metabolism. Moreover, HTs are using the EtOH to obtain carbon in the citric acid cycle, thus, it may be the reason of HT strains surpass high ethanol concentration. Altogether, the knowledge here generated may be used to enrich future discussions about the studied phenomenon and to provide biotechnological development.
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Palavras-chave
Saccharomyces cerevisiae, Bioinformática, Biologia celular, Bioinformatics, Biologia de sistemas, Tolerância ao etanol, Systems biology, Cell biology, Ethanol tolerance