The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging

Chun Zhou, Yun Wang, Yikun Huang, Yongpan An, Xian Fu, Daqian Yang, Yilin Wang, Jintao Zhang, Leslie A. Mitchell, Joel S. Bader, Yizhi Cai, Junbiao Dai, Jef D. Boeke, Zhiming Cai, Zhengwei Xie (), Yue Shen () and Weiren Huang ()
Additional contact information
Chun Zhou: International Cancer Center of Shenzhen University
Yun Wang: BGI Research
Yikun Huang: International Cancer Center of Shenzhen University
Yongpan An: Peking University
Xian Fu: BGI Research
Daqian Yang: Peking University
Yilin Wang: International Cancer Center of Shenzhen University
Jintao Zhang: BGI Research
Leslie A. Mitchell: NYU Langone Health
Joel S. Bader: Johns Hopkins University
Yizhi Cai: 131 Princess Street
Junbiao Dai: Chinese Academy of Sciences
Jef D. Boeke: NYU Langone Health
Zhiming Cai: International Cancer Center of Shenzhen University
Zhengwei Xie: Peking University
Yue Shen: BGI Research
Weiren Huang: International Cancer Center of Shenzhen University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible whole-genome rearrangement on synXIII, we obtain 20 SCRaMbLEd synXIII strains with extended lifespan. Transcriptome analysis reveal the expression of genes involve in global protein synthesis is up-regulated in longer-lived strains. We establish causal links between genotypic change and the long-lived phenotype via reconstruction of some key structural variations observed in post-SCRaMbLE strains and further demonstrate combinatorial effects of multiple aging regulators on lifespan extension. Our findings underscore the potential of synthetic yeasts in unveiling the function of aging-related genes.

Date: 2024
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DOI: 10.1038/s41467-024-54130-3

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