Preventing Production Escape Using an Engineered Glucose-Inducible Genetic Circuit

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Federal do ABC (UFABC)-
Autor(es): dc.creatorTavares, Leonardo F.-
Autor(es): dc.creatorRibeiro, Nathan V.-
Autor(es): dc.creatorZocca, Vitória F. B.-
Autor(es): dc.creatorCorrêa, Graciely G.-
Autor(es): dc.creatorAmorim, Laura A. S.-
Autor(es): dc.creatorLins, Milca R. C. R.-
Autor(es): dc.creatorPedrolli, Danielle B.-
Data de aceite: dc.date.accessioned2025-08-21T20:41:31Z-
Data de disponibilização: dc.date.available2025-08-21T20:41:31Z-
Data de envio: dc.date.issued2025-04-29-
Data de envio: dc.date.issued2023-10-19-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1021/acssynbio.3c00134-
Fonte completa do material: dc.identifierhttps://hdl.handle.net/11449/303868-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/303868-
Descrição: dc.descriptionA proper balance of metabolic pathways is crucial for engineering microbial strains that can efficiently produce biochemicals on an industrial scale while maintaining cell fitness. High production loads can negatively impact cell fitness and hinder industrial-scale production. To address this, fine-tuning gene expression using engineered promoters and genetic circuits can promote control over multiple targets in pathways and reduce the burden. We took advantage of the robust carbon catabolite repression system of Bacillus subtilis to engineer a glucose-inducible genetic circuit that supports growth and production. The circuit is resilient, enabling a quick switch in the production status when exposed to the correct carbon source. By performing serial cultivations for 61 generations under repressive conditions, we preserved the production capacity of the cells, which could be fully accessed by switching to glucose in the next cultivation step. Switching to glucose after 61 generations resulted in 34-fold activation and generated 70% higher production in comparison to standard cultivation in glucose. Conversely, serial cultivation under permanent induction resulted in 62% production loss after 67 generations alongside an increase in the culture growth rate. As a pathway-independent circuit activated by the preferred carbon source, our engineered glucose-inducible genetic circuit is broadly useful and imposes no additional cost to traditional production processes.-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionUniversidade Estadual Paulista (UNESP) School of Pharmaceutical Sciences Department of Bioprocess Engineering and Biotechnology-
Descrição: dc.descriptionFederal University of ABC (UFABC) Center for Natural and Human Sciences, Campus Santo André-
Descrição: dc.descriptionUniversidade Estadual Paulista (UNESP) School of Pharmaceutical Sciences Department of Bioprocess Engineering and Biotechnology-
Formato: dc.format3124-3130-
Idioma: dc.languageen-
Relação: dc.relationACS Synthetic Biology-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectBacillus subtilis-
Palavras-chave: dc.subjectcarbon catabolic repression-
Palavras-chave: dc.subjectgenetic circuit-
Palavras-chave: dc.subjectglucose induction-
Palavras-chave: dc.subjectlong-term fermentation-
Palavras-chave: dc.subjectproduction escape-
Título: dc.titlePreventing Production Escape Using an Engineered Glucose-Inducible Genetic Circuit-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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