Research area
1. Metabolic engineering
In metabolic engineering, enhanced production of value-added chemicals requires precise flux control between growth-essential competing and production pathways, and optimized precursor balance. By engineering genetically tractable strains using these metabolic engineering strategies, efficient conversion of biomass into bioactive compounds, biofuels, and bioplastics can be achieved.
-Escherichia coli
Escherichia coli has been widely regarded as a genetically tractable strain due to its well-characterized genetics, the availability of a wide range of molecular tools, and its high transformation efficiency.
-Vibrio sp.dhg
Brown macroalgae are emerging as a sustainable alternative feedstock with the potential to alleviate concerns about competition for food resources and the limitations of conventional agricultural cultivation. However, about 50% of the carbon components of brown macroalgae are composed of alginate. Most conventional microorganisms cannot metabolize alginate without additional pretreatment, limiting its use as a feedstock. In MDSB lab, we isolated and characterized a fast-growing, alginate-utilizing microorganism, named Vibrio sp. dhg. In contrast to Vibrio natriegens, this strain is capable of robust growth with alginate as the sole carbon source. It has emerged as a promising platform for the efficient conversion of brown macroalgae sugars into diverse value-added biochemicals.-Bacillus,Pseudomonas, and etc.
They are also being engineered, and other novel strains are being identified.
2. Synthetic Biology
Synthetic biology is a emerging research field to redesign and construct the biological parts, devices, and systems for useful and practical purpose.
We are currently developing new molecular tools, and applying these cutting-edge technologies to design and construct high performance microorganism (mainly Escherichia coli, and Vibrio sp.dhg) for the production of biofuels, commodity chemicals, and bioactive compounds including pharmaceutical proteins from renewable biomass.
1) Fine-tunable and predictable expression level control system
- UTR Designer
: It is a computational tool that predicts and designs the mRNA translation initiation region to modulate translation efficiency in prokaryotes.
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Seo SW, Yang JS et al., Metabolic Engineering, 2013
- Repressor library
The repressor library can be constructed by varying the expression levels of the repressor, based on degenerate 5′ UTR sequence variants generated by UTR Library Designer. Modular application of the repressor library enables fine regulation of the flux between the target product biosynthetic pathway and growth-related pathway, thereby enhancing the production of a diverse range of target chemicals.
JY Lee, S Cha, et al., Metabolic Engineering, 2021
2) Enzyme activity engineering based on sequence co-evolution analysis
- sequence co-evolutionary analysis to control the efficiency of enzyme reactions (SCANEER)
: It uses A.A. sequence information as input to find activity-enhancing mutations in distal site from the active site of the enzyme based on sequence co-evolution analysis. By excluding mutations that are likely to cause loss of function of the enzyme, SCANEER facilitates the identification of variants with improved enzymatic activity. Based on the results of SCANEER analysis, we can design high quality library for enzyme engineering.
Kim et al., Metabolic Engineering, 2022
3) Design and Characterization of Biosensors for the high-throughput screening
- RNA-based Biosensor & Protein-based Biosensor
: To engineer an enzyme in the metabolic pathway, the method should be able to associate the enzyme activity with the production of target metabolites, as the ultimate goal of modifying the enzyme in the biosynthetic pathway is to improve metabolite production. In addition, isolation of positive mutants from libraries is the most critical part for directed evolution of enzymes. For these reasons, genetically encoded biosensors composed of biomolecules recognizing metabolites have been proposed and developed. A biosensor is a biological device that detects specific molecules and converts the detection into a measurable signal, like fluorescence intensity or growth-coupled response. By using biosensors, high-throughput screening of metabolite producing microorganisms can be achieved. This approach provides the simple and efficient tool to engineer the pathway enzymes in metabolic engineering.
Seok JY et al., Metabolic Engineering, 2018