Biotechnology: SCRaMbLEing chromosomes to improve yeast

Demonstrations of the SCRaMbLE (Synthetic Chromosome Recombination and Modification by LoxP-Mediated Evolution) system in synthetic chromosomes in yeast to produce rapid strain evolution are presented by the Sc2.0 project in a series of papers in Nature Communications.

Saccharomyces cerevisiae is a commonly-used industrial organism and strains need to be adapted to produce specific products or tolerate harsh industrial conditions. The SCRaMbLE system is designed to generate a large amount of genetic diversity by rearranging genes on a synthetic chromosome with the resulting strains then selected for based on the desired goal, such as improved product synthesis. However, in haploid yeast with only one copy of each chromosome, deletion of essential genes can kill otherwise potentially productive strains.

Jef Boeke and colleagues tackled this problem by mating yeast with synthetic chromosomes to wild-type S. cerevisiae or a closely related species, S. paradoxus. The diploid progeny were more robust than haploid strains, demonstrated by adapting the yeast to grow at 42°C and when exposed to high caffeine levels. The ‘back up’ wild-type chromosomes allowed the diploid yeast to delete essential genes from the synthetic chromosome, which would have been lethal in the original strains.

In another paper, Tom Ellis and colleagues used SCRaMbLE on a yeast strain carrying a fully synthetic chromosome V to improve drug synthesis and adapt the strain to metabolise an alternative sugar source. The team added the biosynthesis pathway for penicillin to their yeast and SCRaMbLE the genome, improving yield two-fold over previous attempts. They also used the technique to evolve yeast strains that can grow on xylose, which is found in high abundance in wood-derived biomass.

On publication, the collection will be available at the following URL: https://www.nature.com/collections/ncomms-syntheticyeast

This collection highlights the experimental work published at Nature Communications on redesigning the S. cerevisiae genome along with commentary from the community about the potential applications and implications of this work for synthetic biology, biotechnology and our understanding of the genome.