Precise control of SCRaMbLE in synthetic haploid and diploid yeast.

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

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.

Journal: Nature communications
DOI: 10.1038/s41467-018-03084-4
Year: 2018

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