2. Academic Validation
  3. Synthetic refactor of essential genes decodes functionally constrained sequences in yeast genome

Synthetic refactor of essential genes decodes functionally constrained sequences in yeast genome

  • iScience. 2022 Aug 18;25(9):104982. doi: 10.1016/j.isci.2022.104982.
Zhenzhen Liang 1,  Zhouqing Luo 1 2,  Weimin Zhang 1 3,  Kang Yu 1,  Hui Wang 1 2,  Binan Geng 4,  Qing Yang 4,  Zuoyu Ni 1,  Cheng Zeng 1,  Yihui Zheng 5,  Chunyuan Li 5,  Shihui Yang 4,  Yingxin Ma 1,  Junbiao Dai 1 5
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Quantitative Engineering Biology, Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • 2 State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China.
  • 3 Institute for Systems Genetics and Department of Biochemistry and Molecular Pharmacology, New York University Langone Medical Center, New York, NY 10011, USA.
  • 4 Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Environmental Microbial Technology Center of Hubei Province, Hubei Key Laboratory of Industrial Biotechnology, College of Life Sciences, Hubei University, Wuhan 430062, China.
  • 5 Key Laboratory for Industrial Biocatalysis (Ministry of Education) and Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
PMID: 36093046 DOI: 10.1016/j.isci.2022.104982
Abstract

The relationship between gene sequence and function matters for fundamental and practical reasons. Here, yeast essential genes were systematically refactored to identify invariable sequences in the coding and regulatory regions. The coding sequences were synonymously recoded with all optimal codons to explore the importance of codon choice. The promoters and terminators were swapped with well-characterized CYC1 promoter and terminator to examine whether a specialized expression is required for the function of a specific gene. Among the 10 essential genes from Chr.XIIL, this scheme successfully generated 7 refactored genes that can effectively support wild-type-like fitness under various conditions, thereby revealing amazing sequence plasticity of yeast genes. Moreover, different invariable elements were identified from the remaining 3 genes, exampling the logics for genetic information encoding and regulation. Further refactoring of all essential genes using this strategy will generate comprehensive understanding of gene sequence choice, thereby guiding its design in various applications.

Keywords

Bioengineering; Genomics; Omics; Synthetic biology.

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