Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/73774
Título: | Model-guided development of an evolutionarily stable yeast chassis |
Autor(es): | Pereira, Filipa Lopes, Hélder Maia, Paulo Meyer, Britta Nocon, Justyna Jouhten, Paula Konstantinidis, Dimitrios Kafkia, Eleni Rocha, Miguel Kötter, Peter Rocha, I. Patil, Kiran R |
Palavras-chave: | Adaptive laboratory evolution Chassis cell Metabolic engineering Multi-objective optimization Systems biology |
Data: | Jul-2021 |
Editora: | Wiley-Blackwell |
Revista: | Molecular Systems Biology |
Citação: | Pereira, Filipa; Lopes, Hélder; Maia, Paulo; Meyer, Britta; Nocon, Justyna; Jouhten, Paula; Konstantinidis, Dimitrios; Kafkia, Eleni; Rocha, Miguel; Kötter, Peter; Rocha, Isabel; Patil, Kiran R, Model-guided development of an evolutionarily stable yeast chassis. Molecular Systems Biology, 17(7), e10253, 2021 |
Resumo(s): | Abstract First-principle metabolic modelling holds potential for designing microbial chassis that are resilient against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has rarely been put to rigorous experimental test. Here, we report the development of Saccharomyces cerevisiae chassis strains for dicarboxylic acid production using genome-scale metabolic modelling. The chassis strains, albeit geared for higher flux towards succinate, fumarate and malate, do not appreciably secrete these metabolites. As predicted by the model, introducing product-specific TCA cycle disruptions resulted in the secretion of the corresponding acid. Adaptive laboratory evolution further improved production of succinate and fumarate, demonstrating the evolutionary robustness of the engineered cells. In the case of malate, multi-omics analysis revealed a flux bypass at peroxisomal malate dehydrogenase that was missing in the yeast metabolic model. In all three cases, flux balance analysis integrating transcriptomics, proteomics and metabolomics data confirmed the flux re-routing predicted by the model. Taken together, our modelling and experimental results have implications for the computer-aided design of microbial cell factories. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/73774 |
DOI: | 10.15252/msb.202110253 |
ISSN: | 1744-4292 |
Versão da editora: | https://www.embopress.org/journal/17444292 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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document_54554_1.pdf Acesso restrito! | 2,26 MB | Adobe PDF | Ver/Abrir |
Este trabalho está licenciado sob uma Licença Creative Commons