Precise control of SCRaMbLE in synthetic haploid and diploid yeast

被引：108

作者：

Jia, Bin ^{[1
,2
]}

Wu, Yi ^{[1
,2
]}

Li, Bing-Zhi ^{[1
,2
]}

Mitchell, Leslie A. ^{[3
]}

Liu, Hong ^{[1
,2
]}

Pan, Shuo ^{[1
,2
]}

Wang, Juan ^{[1
,2
]}

Zhang, Hao-Ran ^{[1
,2
]}

Jia, Nan ^{[1
,2
]}

Li, Bo ^{[1
,2
]}

Shen, Michael ^{[3
]}

Xie, Ze-Xiong ^{[1
,2
]}

Liu, Duo ^{[1
,2
]}

Cao, Ying-Xiu ^{[1
,2
]}

Li, Xia ^{[1
,2
]}

Zhou, Xiao ^{[1
,2
]}

Qi, Hao ^{[1
,2
]}

Boeke, Jef D. ^{[3
]}

Yuan, Ying-Jin ^{[1
,2
]}

机构：

[1] Tianjin Univ, Sch Chem Engn & Technol, Minist Educ, Key Lab Syst Bioengn, Tianjin 300072, Peoples R China

[2] Collaborat Innovat Ctr Chem Sci & Engn Tianjin, SynBio Res Platform, Tianjin 300072, Peoples R China

[3] NYU, Inst Syst Genet, Langone Med Ctr, 550 First Ave, New York, NY 10016 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金; 美国国家科学基金会;

关键词：

CENTRAL CARBON METABOLISM; BETA-CAROTENE PRODUCTION; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; PATHWAY; DIVERSITY; EVOLUTION; SYSTEM; BIOCONTAINMENT; TRANSFORMATION;

D O I：

10.1038/s41467-018-03084-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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