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Synthetic platforms for ad libitum remodelling of yeast central metabolism

Periodic Reporting for period 3 - AdLibYeast (Synthetic platforms for ad libitum remodelling of yeast central metabolism)

Reporting period: 2018-09-01 to 2020-02-29

Replacement of petrochemistry by bio-based processes is key to sustainable development and requires microbes equipped with outstanding, novel-to-nature capabilities. Constructing such advanced ‘cell factories’ requires large-scale remodelling of their core machinery, and therefore of their genome. However, microbes often harbour mosaic genomes in which thousands of genes are scattered over dozens of chromosomes. This absence of a modular organization tremendously restricts genetic accessibility and defies current technologies. To tackle this limitation we develop microbial platforms with specialized, interchangeable synthetic chromosomes that will enable the core machinery to be remodeled at will. Access to a sheer endless variety of configurations of core metabolism offers unique, new possibilities for fundamental understanding and rational engineering of microbes. Our research paves the way for a modular approach to engineering of microbial cells.
During this past period we explored the possibilities to improve the genetic accessibility of the baker’s yeast S. cerevisiae. We have developed methods based on CRISPR-Cas systems enabling to rapidly, efficiently and reliably edit yeast genomic DNA at multiple places simultaneously. Furthermore, we have expanded yeast genetic toolbox by supplying a large set of genetic parts (promoters) issued from related yeast species, which enables to offer a better control of gene expression. Altogether these scientific advances simplify the modification of baker’s yeast genome, thereby facilitating the construction of powerful cell factories.
This project has developed new techniques for genome editing and has considerably increased baker’s yeast genetic toolbox for both fundamental and applied research.