A supernumerary designer chromosome for modular in vivo pathway assembly in Saccharomyces cerevisiae
| Autor: | Pascale Daran-Lapujade, Sofia Dashko, Jean-Marc Daran, Marcel van den Broek, Eline D. Postma, Shannara K. Taylor Parkins, Lars van Breemen |
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| Rok vydání: | 2021 |
| Předmět: |
AcademicSubjects/SCI00010
Computer science In silico Cell Saccharomyces cerevisiae Computational biology Genome Chromosomes Genome engineering 03 medical and health sciences chemistry.chemical_compound Narese/1 medicine Genetics Cell Engineering 030304 developmental biology 0303 health sciences biology 030306 microbiology business.industry Chromosome Modular design biology.organism_classification Transformation (genetics) ComputingMethodologies_PATTERNRECOGNITION medicine.anatomical_structure chemistry Synthetic Biology and Bioengineering business Homologous recombination Glycolysis DNA |
| Zdroj: | Nucleic Acids Research Nucleic acids research, 49(3) |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | The construction of microbial cell factories for sustainable production of chemicals and pharmaceuticals requires extensive genome engineering. UsingSaccharomyces cerevisiae, this study proposes Synthetic Chromosomes (SynChs) as orthogonal expression platforms for rewiring native cellular processes and implementing new functionalities. Capitalizing the powerful homologous recombination capability ofS. cerevisiae, modular SynChs of 50 and 100 Kb were fully assembledde novofrom up to 44 transcriptional-unit-sized fragments in a single transformation. These assemblies were remarkably efficient and faithful to theirin silicodesign. SynChs made of non-coding DNA were stably replicated and segregated irrespective of their size without affecting the physiology of their host. These non-coding SynChs were successfully used as landing pad and as exclusive expression platform for the essential glycolytic pathway. This work pushes the limit of DNA assembly inS. cerevisiaeand paves the way forde novodesigner chromosomes as modular genome engineering platforms inS. cerevisiae. |
| Databáze: | OpenAIRE |
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