 ▲ Research team of Professor Sang-Woo Seo, Department of Chemical and Biological Engineering, College of Engineering, Seoul National University (Photo: Courtesy of Seoul National University College of Engineering) © Wooridul News Reporter Sang-jin Park |
Seoul National University College of Engineering (Dean Kook-Heon Cha) has developed the original technology for designing a gene expression system for high-quality microbial protein production that can be applied to significantly improve the efficiency of biorefinery, from biopharmaceuticals to industrial enzyme production, to carbon-neutral biorefinery. It was revealed on the 5th.
Recombinant proteins are used in various industrial fields, from biopharmaceuticals such as insulin to industrial proteins such as laundry detergents. Because proteins can perform their functions only when they have the perfect length and structure, recombinant proteins synthesized in microorganisms are used after several steps of purification. Until now, as a method of increasing the yield of the production process, strain improvement techniques have been developed to increase the expression level of the target protein or to supplement the insufficient amino acids in cells.
However, in the gene expression system of microorganisms where’transcription’ and’translation’ occur at the same time, if a problem occurs in the transcription process, it is translated as it is to synthesize an incomplete protein. When the expression level is increased by engineering, the amount of incomplete protein synthesized from the damaged template (mRNA) also increases.
The Protein Quality Control System (ProQC), newly developed by Professor Sang-Woo Seo’s team, is a high-quality protein production system that allows only intact mRNA to be used as a template by understanding the existing expression system and redesigning newly discovered biological components. In eukaryotic cells, translation is initiated from mRNA that has been transcribed, and by mimicking this, trigger RNA is expressed as an improved form of trans-activating RNA so that the 3’end regulates the initiation of translation even in microorganisms. Translation is initiated while unraveling the RNA structure through the proper binding), and the trigger sequence was inserted in the form of cis at the 3’end of the mRNA.
In the redesigned expression system, when the transcription process is finished, the cis-trigger at the 3’end is exposed, and this same cis-trigger releases the structure (which inhibits translation initiation) at the 5’end of the same mRNA, and protein synthesis begins. At this time, the mRNA becomes circular with a part of the 5’end sequence and a part of the 3’end sequence bound.
As a result of applying the ProQC system, a new gene expression system, to various proteins, the microorganisms with the developed DNA cassette synthesized 150% to 250% more proteins of full length, and the improvement effect as more incomplete proteins are synthesized in the natural expression system. Appeared more clearly.
In order to confirm the practicality of the ProQC system, the researchers introduced it into the biosynthetic pathway of various metabolites and confirmed that the productivity of metabolites increased by more than two times in the microorganisms applying the ProQC system compared to the existing system even though only the expression cassette of the target protein was changed.
Prof. Sang-Woo Seo said, “The gene expression system developed in this study allows microorganisms to selectively synthesize only high-quality proteins, and it is a new technology that can be added one step further to the existing recombinant protein production strategy. It will dramatically improve the economics and efficiency of the production process of bio-compounds for carbon neutrality and recombinant proteins including industrial enzymes.”
The research results were published online on February 5, in’Nature Chemical Biology’, the world’s most prestigious scientific journal. This research achievement was carried out with support from the Korea Research Foundation’s Korea Bio-Medical Technology Development Korea Bio Grand Challenge project, C1 gas refinery project, and basic laboratory support project.
◇Thesis name and author information
Paper Name: Synthetic protein quality control to enhance full-length translation in bacteria
Publication: Nature Chemical Biology (2021)
DOI: 10.1038/s41589-021-00736-3
First Author: Jin-ah Yang (Senior Researcher, Seoul National University), Yonghee Han (Seoul National University Ph.D.)
Corresponding Author: Sang-Woo Seo (Department of Chemical and Biological Engineering, Seoul National University)
(Seoul = Newswire)