Development of Reproducible high cell density operations for Heterologous Saccharomyces cerevisiae fermentation processes
| dc.catalogador | grr | |
| dc.contributor.advisor | Pérez C., José Ricardo | |
| dc.contributor.advisor | Agosin Trumper, Eduardo | |
| dc.contributor.author | Ibañez Espinel, Francisco | |
| dc.contributor.other | Pontificia Universidad Católica de Chile. Escuela de Ingeniería | |
| dc.date.accessioned | 2024-11-22T15:57:36Z | |
| dc.date.available | 2024-11-22T15:57:36Z | |
| dc.date.issued | 2024 | |
| dc.description | Tesis (Doctor in Engineering Sciences)--Pontificia Universidad Católica de Chile, 2024. | |
| dc.description.abstract | Saccharomyces cerevisiae (SC) is widely used in biotechnology to produce high-value indus trial compounds. Among its advantages are: a known genomic sequence, defined nutritional re quirements, and the ability to grow at high cellular densities. However, reaching densities above 100 g/L is challenging due to the Crabtree effect or metabolic overflow, which can result in ethanolproduction, an inhibitor of cell growth.To address this issue, automatic control strategies have been developed aiming to keep growthbelow the critical specific growth rate. These strategies largely rely on stationary or dynamicmodels, either based on first principles or black-box approaches. In general, the models strive toaccurately reflect the actual behavior of biomass and key metabolites associated with SC growth,emphasizing precision and simplicity.Despite the existence of experimentally validated advanced control schemes, consistently reach ing biomass concentrations of 100 g/L has not been achieved. Furthermore, many of these strate gies employ instrumentation not typically available in industrial bioreactors, either due to their highcost or insufficient reliability. Therefore, to optimize SC cultivation, it’s essential to develop ad vanced automatic control strategies using reliable measurements commonly available in industrialbioreactors (O2 gas, CO2 gas, pH, T, DO, among others).The primary objective of this thesis was to design an automatic operating system for manag ing SC cultures, aiming to achieve high cellular densities consistently and reproducibly. Initially,the development of a dynamic model was proposed to simulate the various observable metabolicstates in an SC culture with cellular densities above 100 g/L. This model was later integrated withadvanced control techniques, considering real conditions and potential measurement noise. Fi nally, a state observer was designed to estimate metabolites not directly measurable, crucial foroptimizing the controller. The production of carotenogenic recombinant SC strains was used as acase study, providing a relevant platform for effective and reproducible operation demonstration ofhigh-density cultures. | |
| dc.fechaingreso.objetodigital | 2024-11-22 | |
| dc.format.extent | xi, 143 páginas | |
| dc.fuente.origen | SRIA | |
| dc.identifier.doi | 10.7764/tesisUC/ING/88647 | |
| dc.identifier.uri | https://doi.org/10.7764/tesisUC/ING/88647 | |
| dc.identifier.uri | https://repositorio.uc.cl/handle/11534/88647 | |
| dc.information.autoruc | Escuela de Ingeniería; Pérez C., José Ricardo; 0000-0002-1278-7782; 100130 | |
| dc.information.autoruc | Escuela de Ingeniería; Agosin Trumper, Eduardo; 0000-0003-1656-150X; 99630 | |
| dc.information.autoruc | Escuela de Ingeniería; Ibañez Espinel, Francisco; 0000-0002-5626-7615; 1071066 | |
| dc.language.iso | en | |
| dc.nota.acceso | Contenido parcial | |
| dc.rights | acceso abierto | |
| dc.subject | Accharomyces cerevisiae | |
| dc.subject | High cell density | |
| dc.subject | Advanced control | |
| dc.subject | State observers | |
| dc.subject.ddc | 500 | |
| dc.subject.dewey | Ciencias | es_ES |
| dc.title | Development of Reproducible high cell density operations for Heterologous Saccharomyces cerevisiae fermentation processes | |
| dc.type | tesis doctoral | |
| sipa.codpersvinculados | 100130 | |
| sipa.codpersvinculados | 99630 | |
| sipa.codpersvinculados | 1071066 |