Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome

Blount, B. A.; Gowers, G-O. F.; Ho, J. C. H.; Ledesma-Amaro, R.; Jovicevic, D.; McKiernan, R. M.; Xie, Z. X.; Li, B. Z.; Yuan, Y. J.; Ellis, T.

Abstract

© 2018 The Author(s). Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.

Citation

Blount, B. A., Gowers, G. F., Ho, J. C. H., Ledesma-Amaro, R., Jovicevic, D., McKiernan, R. M., …Ellis, T. (2018). Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome. Nature Communications, 9(1), Article 1932. https://doi.org/10.1038/s41467-018-03143-w

• Journal Article Type: Article
• Acceptance Date: Jan 23, 2018
• Online Publication Date: May 22, 2018
• Publication Date: 2018-12
• Deposit Date: Jun 3, 2020
• Publicly Available Date: Jun 3, 2020
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 1932
• DOI: https://doi.org/10.1038/s41467-018-03143-w
• Keywords: General Biochemistry, Genetics and Molecular Biology; General Physics and Astronomy; General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/4176483
• Publisher URL: https://www.nature.com/articles/s41467-018-03143-w