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

doi:10.1038/s41467-018-03084-4

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

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Article number	1933
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03084-4
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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title = "Precise control of SCRaMbLE in synthetic haploid and diploid yeast",

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.",

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

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doi = "10.1038/s41467-018-03084-4",

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AU - Jia, Bin

AU - Wu, Yi

AU - Li, Bing Zhi

AU - Mitchell, Leslie A.

AU - Liu, Hong

AU - Pan, Shuo

AU - Wang, Juan

AU - Zhang, Hao Ran

AU - Jia, Nan

AU - Li, Bo

AU - Shen, Michael

AU - Xie, Ze Xiong

AU - Liu, Duo

AU - Cao, Ying Xiu

AU - Li, Xia

AU - Zhou, Xiao

AU - Qi, Hao

AU - Boeke, Jef D.

AU - Yuan, Ying Jin

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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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Precise control of SCRaMbLE in synthetic haploid and diploid yeast

Abstract

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