Precise control of SCRaMbLE in synthetic haploid and diploid yeast

Bin Jia, Yi Wu, Bing Zhi Li, Leslie A. Mitchell, Hong Liu, Shuo Pan, Juan Wang, Hao Ran Zhang, Nan Jia, Bo Li, Michael Shen, Ze Xiong Xie, Duo Liu, Ying Xiu Cao, Xia Li, Xiao Zhou, Hao Qi, Jef D. Boeke, Ying Jin Yuan

    Research output: Contribution to journalArticle

    Abstract

    Compatibility between host cells and heterologous pathways is a challenge for constructing organisms with high productivity or gain of function. Designer yeast cells incorporating the Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system provide a platform for generating genotype diversity. Here we construct a genetic AND gate to enable precise control of the SCRaMbLE method to generate synthetic haploid and diploid yeast with desired phenotypes. The yield of carotenoids is increased to 1.5-fold by SCRaMbLEing haploid strains and we determine that the deletion of YEL013W is responsible for the increase. Based on the SCRaMbLEing in diploid strains, we develop a strategy called Multiplex SCRaMbLE Iterative Cycling (MuSIC) to increase the production of carotenoids up to 38.8-fold through 5 iterative cycles of SCRaMbLE. This strategy is potentially a powerful tool for increasing the production of bio-based chemicals and for mining deep knowledge.

    Original languageEnglish (US)
    Article number1933
    JournalNature communications
    Volume9
    Issue number1
    DOIs
    StatePublished - Dec 1 2018

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

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  • Cite this

    Jia, B., Wu, Y., Li, B. Z., Mitchell, L. A., Liu, H., Pan, S., Wang, J., Zhang, H. R., Jia, N., Li, B., Shen, M., Xie, Z. X., Liu, D., Cao, Y. X., Li, X., Zhou, X., Qi, H., Boeke, J. D., & Yuan, Y. J. (2018). Precise control of SCRaMbLE in synthetic haploid and diploid yeast. Nature communications, 9(1), [1933]. https://doi.org/10.1038/s41467-018-03084-4