Format

Send to

Choose Destination
Nat Commun. 2018 May 22;9(1):1933. doi: 10.1038/s41467-018-03084-4.

Precise control of SCRaMbLE in synthetic haploid and diploid yeast.

Jia B1,2, Wu Y1,2, Li BZ1,2, Mitchell LA3, Liu H1,2, Pan S1,2, Wang J1,2, Zhang HR1,2, Jia N1,2, Li B1,2, Shen M3, Xie ZX1,2, Liu D1,2, Cao YX1,2, Li X1,2, Zhou X1,2, Qi H1,2, Boeke JD3, Yuan YJ4,5.

Author information

1
Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.
2
SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China.
3
Institute for Systems Genetics, New York University Langone Medical Center, 550 First Avenue, New York, NY, 10016, USA.
4
Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China. yjyuan@tju.edu.cn.
5
SynBio Research Platform, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, 300072, China. yjyuan@tju.edu.cn.

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.

PMID:
29789567
PMCID:
PMC5964104
DOI:
10.1038/s41467-018-03084-4
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center