Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico

Detalhes bibliográficos
Autor(a) principal: Harth, Matheus Lopes
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/18462
Resumo: Hyaluronic acid is a biopolymer found in many organisms, which has several biomedical applications, like viscosupplementation and aesthetic procedures. Such applications are associated with its rheological properties, that depend directly on the molar mass. Streptococcus zooepidemicus bacteria can produce hyaluronic acid. However, it is still necessary to determine the best operating conditions for a bioreactor so that higher HA yields are achieved. In the light of this, our work aims to develop kinetic and genome-scale models that describe the microbial production of hyaluronic acid. To reach this objective, information was collected regarding the central carbon metabolism, production, and consumption of amino acids of S. zooepidemicus. To adjust and validate these models, experimental data were obtained from cultures using glucose as carbon source and soybean peptone as nitrogen source in 5 L automated stirred tank bioreactor. To adjust the kinetic model, PSO algorithm was used, while OptFlux software was used to simulate the developed genome-scale model. The agitated tank bioreactor cultures indicated the microorganism consumed other nutrients present in the peptone besides the glucose added to the medium. In addition, an adaptation phase of almost 20 h. This phase was reduced by increasing the concentration of glucose in the inoculum and pre-inoculum. The experimental results also showed that the concentration of amino acids increases at the end of the culture, which can be explained by the action of proteases. Regarding the proposed kinetic model, it could competently describe most of the experimental data, diverging in the last data of cell and lactic acid concentration. This fact is attributed to the more intense consumption of the nutrients of the peptone used. As for the adapted genomic scale model, the major alterations were regarding the reactions related to the formation of acid D- glucuronic and the biosynthesis and consumption of amino acids. The validation tests results diverged from the experimental data. It is possible that consumption of other nutrients in the peptone were responsible for this. However, errors that compromised the simulations were not observed, indicating the developed genome-scale model potential.
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spelling Harth, Matheus LopesHorta, Antonio Carlos Lupernihttp://lattes.cnpq.br/5923938048634505Giordano, Roberto de Camposhttp://lattes.cnpq.br/42854668392759467ccdba4c-3970-4dc4-bb13-95b13057eb792023-08-30T10:50:33Z2023-08-30T10:50:33Z2018-03-01HARTH, Matheus Lopes. Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico. 2018. Dissertação (Mestrado em Engenharia Química) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18462.https://repositorio.ufscar.br/handle/ufscar/18462Hyaluronic acid is a biopolymer found in many organisms, which has several biomedical applications, like viscosupplementation and aesthetic procedures. Such applications are associated with its rheological properties, that depend directly on the molar mass. Streptococcus zooepidemicus bacteria can produce hyaluronic acid. However, it is still necessary to determine the best operating conditions for a bioreactor so that higher HA yields are achieved. In the light of this, our work aims to develop kinetic and genome-scale models that describe the microbial production of hyaluronic acid. To reach this objective, information was collected regarding the central carbon metabolism, production, and consumption of amino acids of S. zooepidemicus. To adjust and validate these models, experimental data were obtained from cultures using glucose as carbon source and soybean peptone as nitrogen source in 5 L automated stirred tank bioreactor. To adjust the kinetic model, PSO algorithm was used, while OptFlux software was used to simulate the developed genome-scale model. The agitated tank bioreactor cultures indicated the microorganism consumed other nutrients present in the peptone besides the glucose added to the medium. In addition, an adaptation phase of almost 20 h. This phase was reduced by increasing the concentration of glucose in the inoculum and pre-inoculum. The experimental results also showed that the concentration of amino acids increases at the end of the culture, which can be explained by the action of proteases. Regarding the proposed kinetic model, it could competently describe most of the experimental data, diverging in the last data of cell and lactic acid concentration. This fact is attributed to the more intense consumption of the nutrients of the peptone used. As for the adapted genomic scale model, the major alterations were regarding the reactions related to the formation of acid D- glucuronic and the biosynthesis and consumption of amino acids. The validation tests results diverged from the experimental data. It is possible that consumption of other nutrients in the peptone were responsible for this. However, errors that compromised the simulations were not observed, indicating the developed genome-scale model potential.O ácido hialurônico é um biopolímero encontrado em diversos organismos e que possui diversas aplicações biomédicas, como viscossuplementação em articulações e procedimentos estéticos. Tais aplicações estão associadas com suas propriedades reológicas, que dependem diretamente da massa molar. As bactérias Streptococcus zooepidemicus são capazes de produzir ácido hialurônico, no entanto, ainda é preciso determinar as melhores condições de operação do biorreator de modo que se obtenha maiores rendimentos de ácido hialurônico. Em vista disto, o presente trabalho tem como objetivo desenvolver modelos cinéticos e de escala genômica que descrevam a produção microbiana de ácido hialurônico. Para isso, foram levantadas informações a respeito do metabolismo do carbono central, de produção e consumo de aminoácidos do microrganismo S. zooepidemicus. Para ajustar e validar estes modelos, foram obtidos dados experimentais de cultivos usando glicose como fonte de carbono e peptona de soja como fonte de nitrogênio em biorreator automatizado tipo tanque agitado de 5 L. Para ajustar o modelo cinético foi utilizado o algoritmo PSO, enquanto que, para simular o modelo de escala genômica desenvolvido foi utilizado o software OptFlux. Os cultivos em biorreator tipo tanque agitado indicaram que o microrganismo consumiu outros açúcares presentes na peptona além da glicose adicionada ao meio, além de ser observada uma fase de adaptação de quase 20 h. Esta fase foi posteriormente reduzida ao se conduzir as etapas de pré-inóculo e inóculo usando concentrações mais altas de fonte de carbono. Além disso, os resultados experimentais mostraram que a concentração de aminoácidos aumenta no final do cultivo, que pode ser explicado por conta da ação de proteases. Em relação ao modelo cinético proposto, ele consegue descrever com competência a maioria dos dados experimentais, divergindo nos últimos dados de concentração celular e ácido lático. Atribui-se este fato ao consumo mais intenso dos nutrientes da peptona utilizada. Quanto ao modelo de escala genômica adaptado, as principais alterações foram na adição de reações relacionadas à formação de ácido D-glicurônico e nas vias de biossíntese e consumo de alguns aminoácidos. Os resultados das simulações feitas para validar o modelo mostraram divergências com os dados experimentais. Acredita-se que isto seja decorrente do consumo de outros nutrientes presentes na peptona de soja utilizada, entretanto, destaca-se que não foram observados erros que comprometessem as simulações feitas, o que indica o potencial que o modelo de escala genômica desenvolvido possui.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Processo 132377/2017-9 CNPqporUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Engenharia Química - PPGEQUFSCarAttribution-NonCommercial-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-nd/3.0/br/info:eu-repo/semantics/openAccessModelo de escala genômicaÁcido hialurônicoStreptococcus zooepidemicusProteaseModelo cinéticoBiorreatorGenome-scale modelHyaluronic acidKinetic modelBioreactorENGENHARIAS::ENGENHARIA QUIMICACultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônicoCultivation of Streptococcus zooepidemicus: modeling and hyaluronic acid productioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis600600e2d68a62-20dd-44a1-a955-70b9eb98a9ecreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissertação MLH.pdfDissertação MLH.pdfDissertaçãoapplication/pdf3446414https://repositorio.ufscar.br/bitstream/ufscar/18462/3/Disserta%c3%a7%c3%a3o%20MLH.pdfc555eebd88171a167c2b08970d6208deMD53CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8810https://repositorio.ufscar.br/bitstream/ufscar/18462/4/license_rdff337d95da1fce0a22c77480e5e9a7aecMD54TEXTDissertação MLH.pdf.txtDissertação MLH.pdf.txtExtracted texttext/plain143100https://repositorio.ufscar.br/bitstream/ufscar/18462/5/Disserta%c3%a7%c3%a3o%20MLH.pdf.txtfdd87da27de37b52c69145941b801632MD55ufscar/184622024-05-14 18:30:38.283oai:repositorio.ufscar.br:ufscar/18462Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222024-05-14T18:30:38Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
dc.title.alternative.eng.fl_str_mv Cultivation of Streptococcus zooepidemicus: modeling and hyaluronic acid production
title Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
spellingShingle Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
Harth, Matheus Lopes
Modelo de escala genômica
Ácido hialurônico
Streptococcus zooepidemicus
Protease
Modelo cinético
Biorreator
Genome-scale model
Hyaluronic acid
Kinetic model
Bioreactor
ENGENHARIAS::ENGENHARIA QUIMICA
title_short Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
title_full Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
title_fullStr Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
title_full_unstemmed Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
title_sort Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico
author Harth, Matheus Lopes
author_facet Harth, Matheus Lopes
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/4285466839275946
dc.contributor.author.fl_str_mv Harth, Matheus Lopes
dc.contributor.advisor1.fl_str_mv Horta, Antonio Carlos Luperni
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5923938048634505
dc.contributor.advisor-co1.fl_str_mv Giordano, Roberto de Campos
dc.contributor.authorID.fl_str_mv 7ccdba4c-3970-4dc4-bb13-95b13057eb79
contributor_str_mv Horta, Antonio Carlos Luperni
Giordano, Roberto de Campos
dc.subject.por.fl_str_mv Modelo de escala genômica
Ácido hialurônico
Streptococcus zooepidemicus
Protease
Modelo cinético
Biorreator
topic Modelo de escala genômica
Ácido hialurônico
Streptococcus zooepidemicus
Protease
Modelo cinético
Biorreator
Genome-scale model
Hyaluronic acid
Kinetic model
Bioreactor
ENGENHARIAS::ENGENHARIA QUIMICA
dc.subject.eng.fl_str_mv Genome-scale model
Hyaluronic acid
Kinetic model
Bioreactor
dc.subject.cnpq.fl_str_mv ENGENHARIAS::ENGENHARIA QUIMICA
description Hyaluronic acid is a biopolymer found in many organisms, which has several biomedical applications, like viscosupplementation and aesthetic procedures. Such applications are associated with its rheological properties, that depend directly on the molar mass. Streptococcus zooepidemicus bacteria can produce hyaluronic acid. However, it is still necessary to determine the best operating conditions for a bioreactor so that higher HA yields are achieved. In the light of this, our work aims to develop kinetic and genome-scale models that describe the microbial production of hyaluronic acid. To reach this objective, information was collected regarding the central carbon metabolism, production, and consumption of amino acids of S. zooepidemicus. To adjust and validate these models, experimental data were obtained from cultures using glucose as carbon source and soybean peptone as nitrogen source in 5 L automated stirred tank bioreactor. To adjust the kinetic model, PSO algorithm was used, while OptFlux software was used to simulate the developed genome-scale model. The agitated tank bioreactor cultures indicated the microorganism consumed other nutrients present in the peptone besides the glucose added to the medium. In addition, an adaptation phase of almost 20 h. This phase was reduced by increasing the concentration of glucose in the inoculum and pre-inoculum. The experimental results also showed that the concentration of amino acids increases at the end of the culture, which can be explained by the action of proteases. Regarding the proposed kinetic model, it could competently describe most of the experimental data, diverging in the last data of cell and lactic acid concentration. This fact is attributed to the more intense consumption of the nutrients of the peptone used. As for the adapted genomic scale model, the major alterations were regarding the reactions related to the formation of acid D- glucuronic and the biosynthesis and consumption of amino acids. The validation tests results diverged from the experimental data. It is possible that consumption of other nutrients in the peptone were responsible for this. However, errors that compromised the simulations were not observed, indicating the developed genome-scale model potential.
publishDate 2018
dc.date.issued.fl_str_mv 2018-03-01
dc.date.accessioned.fl_str_mv 2023-08-30T10:50:33Z
dc.date.available.fl_str_mv 2023-08-30T10:50:33Z
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dc.identifier.citation.fl_str_mv HARTH, Matheus Lopes. Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico. 2018. Dissertação (Mestrado em Engenharia Química) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18462.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/18462
identifier_str_mv HARTH, Matheus Lopes. Cultivo de Streptococcus zooepidemicus: modelagem e produção de ácido hialurônico. 2018. Dissertação (Mestrado em Engenharia Química) – Universidade Federal de São Carlos, São Carlos, 2018. Disponível em: https://repositorio.ufscar.br/handle/ufscar/18462.
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