Full humanization of the glycolytic pathway in Saccharomyces cerevisiae.

Autor:	Boonekamp FJ; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Knibbe E; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Vieira-Lara MA; Laboratory of Pediatrics, Section Systems Medicine and Metabolic Signalling, Center for Liver, Digestive and Metabolic Disease, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Wijsman M; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Luttik MAH; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., van Eunen K; Laboratory of Pediatrics, Section Systems Medicine and Metabolic Signalling, Center for Liver, Digestive and Metabolic Disease, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Ridder MD; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Bron R; Department of Biomedical Engineering-FB40, W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Almonacid Suarez AM; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., van Rijn P; Department of Biomedical Engineering-FB40, W.J. Kolff Institute for Biomedical Engineering and Materials Science-FB41, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Wolters JC; Laboratory of Pediatrics, Section Systems Medicine and Metabolic Signalling, Center for Liver, Digestive and Metabolic Disease, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Pabst M; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Daran JM; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands., Bakker BM; Laboratory of Pediatrics, Section Systems Medicine and Metabolic Signalling, Center for Liver, Digestive and Metabolic Disease, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands., Daran-Lapujade P; Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands. Electronic address: p.a.s.daran-lapujade@tudelft.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Jun 28; Vol. 39 (13), pp. 111010.
DOI:	10.1016/j.celrep.2022.111010
Abstrakt:	Although transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light context-dependent responses. Human hexokinase 1 and 2, but not 4, required mutations in their catalytic or allosteric sites for functionality in yeast, whereas hexokinase 3 was unable to complement its yeast ortholog. Comparison with human tissues cultures showed preservation of turnover numbers of human glycolytic enzymes in yeast and human cell cultures. This demonstration of transplantation of an entire essential pathway paves the way for establishment of species-, tissue-, and disease-specific metazoan models. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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