Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis

Autores
Castañeda, María Teresita; Nuñez, Sebastián; Jamilis Ricaldoni, Martín Ignacio; De Battista, Hernán
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy source mass feed rate (Fin · sr) and its concentration in the feed (sr) based on lipid accumulation targets, and defined minimum feeding flow rate (Fin) according to process duration. We then assessed the impact of these parameters on commonly used bioprocess metrics—lipid yield, titer, productivity, and intracellular accumulation—across wild-type and engineered strains. Our results showed that the selection of Fin · sr was strongly strain-dependent and significantly influenced strain performance. Moreover, for a given Fin · sr, the specific values of sr, and the resulting Fin, had distinct and non-equivalent effects on performance metrics. This methodology enables the rational pre-selection of feeding strategies and strains, improving resource efficiency and reducing the probability of failed experiments.
Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales
Materia
Ingeniería Química
Rhodosporidium toruloides
dynamic flux balance analysis
metabolic model
designed strains
bioprocess performance metrics
fed-batch cultivation
feeding strategies
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/189167
Acceder
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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance AnalysisCastañeda, María TeresitaNuñez, SebastiánJamilis Ricaldoni, Martín IgnacioDe Battista, HernánIngeniería QuímicaRhodosporidium toruloidesdynamic flux balance analysismetabolic modeldesigned strainsbioprocess performance metricsfed-batch cultivationfeeding strategiesFed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy source mass feed rate (Fin · sr) and its concentration in the feed (sr) based on lipid accumulation targets, and defined minimum feeding flow rate (Fin) according to process duration. We then assessed the impact of these parameters on commonly used bioprocess metrics—lipid yield, titer, productivity, and intracellular accumulation—across wild-type and engineered strains. Our results showed that the selection of Fin · sr was strongly strain-dependent and significantly influenced strain performance. Moreover, for a given Fin · sr, the specific values of sr, and the resulting Fin, had distinct and non-equivalent effects on performance metrics. This methodology enables the rational pre-selection of feeding strategies and strains, improving resource efficiency and reducing the probability of failed experiments.Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales2025-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/189167enginfo:eu-repo/semantics/altIdentifier/issn/2311-5637info:eu-repo/semantics/altIdentifier/doi/10.3390/fermentation11060354info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-12-23T11:54:13Zoai:sedici.unlp.edu.ar:10915/189167Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-12-23 11:54:13.943SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
title Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
spellingShingle Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
Castañeda, María Teresita
Ingeniería Química
Rhodosporidium toruloides
dynamic flux balance analysis
metabolic model
designed strains
bioprocess performance metrics
fed-batch cultivation
feeding strategies
title_short Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
title_full Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
title_fullStr Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
title_full_unstemmed Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
title_sort Enhancement of Lipid Production in Rhodosporidium toruloides: Designing Feeding Strategies Through Dynamic Flux Balance Analysis
dc.creator.none.fl_str_mv Castañeda, María Teresita
Nuñez, Sebastián
Jamilis Ricaldoni, Martín Ignacio
De Battista, Hernán
author Castañeda, María Teresita
author_facet Castañeda, María Teresita
Nuñez, Sebastián
Jamilis Ricaldoni, Martín Ignacio
De Battista, Hernán
author_role author
author2 Nuñez, Sebastián
Jamilis Ricaldoni, Martín Ignacio
De Battista, Hernán
author2_role author
author
author
dc.subject.none.fl_str_mv Ingeniería Química
Rhodosporidium toruloides
dynamic flux balance analysis
metabolic model
designed strains
bioprocess performance metrics
fed-batch cultivation
feeding strategies
topic Ingeniería Química
Rhodosporidium toruloides
dynamic flux balance analysis
metabolic model
designed strains
bioprocess performance metrics
fed-batch cultivation
feeding strategies
dc.description.none.fl_txt_mv Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy source mass feed rate (Fin · sr) and its concentration in the feed (sr) based on lipid accumulation targets, and defined minimum feeding flow rate (Fin) according to process duration. We then assessed the impact of these parameters on commonly used bioprocess metrics—lipid yield, titer, productivity, and intracellular accumulation—across wild-type and engineered strains. Our results showed that the selection of Fin · sr was strongly strain-dependent and significantly influenced strain performance. Moreover, for a given Fin · sr, the specific values of sr, and the resulting Fin, had distinct and non-equivalent effects on performance metrics. This methodology enables the rational pre-selection of feeding strategies and strains, improving resource efficiency and reducing the probability of failed experiments.
Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales
description Fed-batch cultivation is a widely used strategy for microbial lipid production, offering flexibility in nutrient control and the potential for high lipid productivity. However, optimizing feeding strategies remains a complex challenge, as it depends on multiple factors, including strain-specific metabolism and process limitations. In this study, we developed a computational framework based on dynamic flux balance analysis and small-scale metabolic models to evaluate and optimize lipid production in Rhodosporidium toruloides strains. We proposed equations to estimate both the carbon and energy source mass feed rate (Fin · sr) and its concentration in the feed (sr) based on lipid accumulation targets, and defined minimum feeding flow rate (Fin) according to process duration. We then assessed the impact of these parameters on commonly used bioprocess metrics—lipid yield, titer, productivity, and intracellular accumulation—across wild-type and engineered strains. Our results showed that the selection of Fin · sr was strongly strain-dependent and significantly influenced strain performance. Moreover, for a given Fin · sr, the specific values of sr, and the resulting Fin, had distinct and non-equivalent effects on performance metrics. This methodology enables the rational pre-selection of feeding strategies and strains, improving resource efficiency and reducing the probability of failed experiments.
publishDate 2025
dc.date.none.fl_str_mv 2025-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/189167
url http://sedici.unlp.edu.ar/handle/10915/189167
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/2311-5637
info:eu-repo/semantics/altIdentifier/doi/10.3390/fermentation11060354
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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