Professor Huang Mingtao's team at the School of Food Science and Engineering, South China University of Technology, has modified the Unfolded Protein Response Element (UPRE) in brewing yeast and applied it for dynamic regulation of gene expression. The related findings were published on April 30th in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) under the title "Tailored UPRE2 variants for dynamic gene regulation in yeast," with South China University of Technology as the sole credited institution.
Brewing yeast is widely used in the field of biomanufacturing, where metabolic engineering can optimize its production performance by effectively directing metabolic flux towards target products. Compared to traditional methods of rigidly increasing or decreasing the expression levels of key genes in metabolic pathways, dynamic gene regulation in response to intracellular and extracellular changes can more effectively coordinate product synthesis with cellular status, thereby enhancing the efficiency of product synthesis. Natural response pathways in brewing yeast, such as the Unfolded Protein Response (UPR), can perceive and respond to environmental changes inside and outside the cell.
However, the natural response elements in yeast are often insufficient in quantity and sensitivity to meet practical application requirements. To overcome this limitation, Professor Huang Mingtao's team has created a diverse set of dynamic responsive regulatory elements for yeast gene expression. By constructing a UPRE2 mutant library and using reporter molecules such as chromoproteins and fluorescent proteins as tools, they successfully identified UPRE2 mutant variants with superior performance. These mutants exhibited greater sensitivity to environmental changes and stronger dynamic control of gene expression intensity compared to the wild-type UPRE2.
The corresponding author of the paper, Huang Mingtao, stated that through in-depth analysis of the mutants, their team discovered for the first time that the highly active mutant UPRE2m has a stronger binding affinity with Hac1, further expanding the understanding of the Unfolded Protein Response mechanism. These UPRE2 mutant variants have plug-and-play characteristics and can be combined with various promoters. When applied to the regulation of key gene expression, these elements significantly increase the yield of target products.
This research was supported by the National Key R&D Program for Green Biomanufacturing, the National Natural Science Foundation of China, and the Special Fund for Basic Scientific Research of Central Universities, among other projects.
Link to the paper: https://doi.org/10.1073/pnas.2315729121
