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Unlocking the formate utilization of wild-type Yarrowia lipolytica through adaptive laboratory evolution
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  • qian chen,
  • Xue Yang,
  • Yunhong Chen,
  • Yuyue Ma,
  • Jianfeng Huang,
  • Zhidan zhang,
  • Yefu Chen ,
  • Yanfei Zhang,
  • Guoping Zhao
qian chen
Tianjin University of Science and Technology
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Yunhong Chen
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Jianfeng Huang
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Zhidan zhang
Tianjin Institute of Industrial Biotechnology
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Yefu Chen
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Yanfei Zhang

Corresponding Author:zhangyf@tib.cas.cn

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Guoping Zhao
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Synthetic biology is contributing to the advancement of the global net-negative carbon economy, with emphasis on formate as a member of the one-carbon substrate garnering substantial attention. In this study, we employed base editing tools to facilitate adaptive evolution, achieving a formate tolerance of Yarrowia lipolytica to 1 M within two months. This effort resulted in two mutant strains, designated as M25-70 and M25-14, both exhibiting significantly enhanced formate utilization capabilities. Transcriptomic analysis revealed the up-regulation of nine endogenous genes encoding formate dehydrogenases when cultivated utilizing formate as the sole carbon source. Furthermore, we uncovered the pivotal role of the glyoxylate and threonine-based serine pathway in enhancing glycine supply to promote formate assimilation. The full potential of Yarrowia lipolytica to tolerate and utilize formate establishing the foundation for pyruvate carboxylase-based carbon sequestration pathways. Importantly, this study highlights the existence of a natural formate metabolic pathway in Yarrowia lipolytica.
29 Apr 2024Submitted to Biotechnology Journal
30 Apr 2024Submission Checks Completed
30 Apr 2024Assigned to Editor
30 Apr 2024Reviewer(s) Assigned
17 May 2024Review(s) Completed, Editorial Evaluation Pending
17 May 2024Editorial Decision: Revise Major
28 May 2024Review(s) Completed, Editorial Evaluation Pending