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Jia, Bin; Wu, Yi; Li, Bing-Zhi; Mitchell, Leslie A; Liu, Hong; Pan, Shuo; Wang, Juan; Zhang, Hao-Ran; Jia, Nan; Li, Bo; Shen, Michael; Xie, Ze-Xiong; Liu, Duo; Cao, Ying-Xiu; Li, Xia; Zhou, Xiao; Qi, Hao; Boeke, Jef D; Yuan, Ying-Jin
Nature communications, 05/2018, Volume: 9, Issue: 1Journal Article
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.
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