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 and Ying-Jin Yuan ()
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Bin Jia: Tianjin University
Yi Wu: Tianjin University
Bing-Zhi Li: Tianjin University
Leslie A. Mitchell: New York University Langone Medical Center
Hong Liu: Tianjin University
Shuo Pan: Tianjin University
Juan Wang: Tianjin University
Hao-Ran Zhang: Tianjin University
Nan Jia: Tianjin University
Bo Li: Tianjin University
Michael Shen: New York University Langone Medical Center
Ze-Xiong Xie: Tianjin University
Duo Liu: Tianjin University
Ying-Xiu Cao: Tianjin University
Xia Li: Tianjin University
Xiao Zhou: Tianjin University
Hao Qi: Tianjin University
Jef D. Boeke: New York University Langone Medical Center
Ying-Jin Yuan: Tianjin University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03084-4

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