Reprogramming methanol utilization pathways to convert Saccharomyces cerevisiae to a synthetic methylotroph
Journal article, 2023
Methanol, an organic one-carbon (C1) compound, represents an attractive alternative carbon source for microbial fermentation. Despite considerable advancements in methanol utilization by prokaryotes such as Escherichia coli, engineering eukaryotic model organisms such as Saccharomyces cerevisiae into synthetic methylotrophs remains challenging. Here, an engineered module circuit strategy combined with adaptive laboratory evolution was applied to engineer S. cerevisiae to use methanol as the sole carbon source. We revealed that the evolved glyoxylate-based serine pathway plays an important role in methanol-dependent growth by promoting formaldehyde assimilation. Further, we determined that the isoprenoid biosynthetic pathway was upregulated, resulting in an increased concentration of squalene and ergosterol in our evolved strain. These changes could potentially alleviate cell membrane damage in the presence of methanol. This work sets the stage for expanding the potential of exploiting S. cerevisiae as a potential organic one-carbon platform for biochemical or biofuel production. [Figure not available: see fulltext.].
Author
Chunjun Zhan
Joint BioEnergy Institute, California
Chalmers, Life Sciences, Systems and Synthetic Biology
Jiangnan University
Lawrence Berkeley National Laboratory
Xiaowei Li
Chalmers, Life Sciences, Systems and Synthetic Biology
Guangxu Lan
Lawrence Berkeley National Laboratory
Joint BioEnergy Institute, California
Edward E.K. Baidoo
Lawrence Berkeley National Laboratory
Joint BioEnergy Institute, California
Yankun Yang
Jiangnan University
Yuzhong Liu
Joint BioEnergy Institute, California
Lawrence Berkeley National Laboratory
Yang Sun
Jiangnan University
Henan University of Chinese Medicine
Shijie Wang
Jiangnan University
Yanyan Wang
Chalmers, Life Sciences, Systems and Synthetic Biology
Guokun Wang
Chalmers, Life Sciences, Systems and Synthetic Biology
Jens B Nielsen
Chalmers, Life Sciences, Systems and Synthetic Biology
BioInnovation Institute
J.D. Keasling
Joint BioEnergy Institute, California
University of California
Lawrence Berkeley National Laboratory
Technical University of Denmark (DTU)
Shenzhen Institutes for Advanced Technologies
Yun Chen
Chalmers, Life Sciences, Systems and Synthetic Biology
Zhonghu Bai
Jiangnan University
Nature Catalysis
25201158 (eISSN)
Vol. 6 5 435-450Subject Categories
Biochemistry and Molecular Biology
Other Chemical Engineering
Microbiology
DOI
10.1038/s41929-023-00957-w