안녕하십니까. 국민대학교 바이오발효융합학과 단백질진화연구실의 연구책임자 서주현교수입니다. 저희 연구실의 이름을 지을 때, 저는 최대한 간략하게 짓고 싶었습니다. 그러나, 이름 속에 숨겨진 scope은 굉장히 넓습니다. ‘단백질’이라는 흔한 단어 속에는 효소 뿐만 아니라 항체, 조절인자도 연구하고자 한다는 의미를 내포하고 있습니다. 이러한 연구 scope 속에서 저희 연구실에서는 효소 진화, 항체 공학, repressor engineering, 대사공학 등을 현재 연구 중입니다. 아래에 좀 더 자세히 말씀드리고자 합니다.

1) 효소 진화: 효소 진화 연구는 필연적으로 high-throughput screening method 개발을 포함하게 됩니다. 저희 연구실에서는 library generation 뿐만 아니라 각 효소의 특성에 맞도록 high-throughput screening method를 개발하여 효소 진화를 하고 있습니다. 만약 high-throughput screening method 개발이 여의치 않은 효소에 대해서는 rational design을 수행하고 있고, 이를 위해서 bioinformatics 분석을 수행하고 있습니다. Bioinformatics 분석은 보편적인 multiple sequence alignment 뿐만 아니라 ancient gene generation, family profile analysis와 같은 분석을 python programming을 활용하여 대용량으로 수행하고 있습니다. 또한, 효소의 구조 분석 및 시뮬레이션을 위해서 protein structure prediction, protein-ligand docking, molecular dynamics 분석을 수행하고 있는데, 이 중 protein structure prediction 툴은 자체적으로 개발한 방법을 사용하고 있습니다. 최근에는 AI model 중 diffusion model을 이용한 protein design 연구도 시작하고 있습니다.

2) 효소진화에 기반한 대사공학: 진화된 효소를 개발한 후, 이를 이용하여 genome engineering을 통해 native 유전자를 변형하여 생산성 향상 등의 phenotype 변화 연구도 수행하고 있습니다. 요즈음은 대장균에서의 CRISPR-Cas 적용은 어디서나 루틴하게 이루어지고 있기 때문에 저희 연구실에서도 이러한 방법들을 적용하여 metabolic flux adjustment 연구도 수행하고 있습니다. 

3) Transcriptional regulator engineering을 통한 biosensor 개발 및 이의 응용: 특정 regulator를 engineering 하여 target compound에 binding 할 수 있도록 만들고 이를 이용하여 high-throughput screening method 혹은 biosensor 로 활용하는 연구를 수행하고 있습니다. Transcriptional regulator는 효소나 항체에 비해 mutation에 취약한데, 이러한 어려운 점을 피하여 우리가 원하는 산물에 binding 할 수 있도록 engineering 하고 있습니다.

4) 항체 공학: 저희 학과에는 동물세포배양을 루틴하게 하는 교수님이 여러분 계시지만, 저희 연구실은 동물세포배양을 해본 적은 없습니다. 그래서 저희는 full-length antibody 보다는 scFv나 nanobody를 활용하여 항체공학 연구를 하고 있습니다. 항체 공학을 위해서는 protein structure prediction 후 protein-protein docking을 통해 interface를 탐색하고 interface에 위치하는 부분에 대해서 deep mutational scanning 법을 적용하는 등으로 binding region에 대해 rational design을 하고 있습니다.

   Prof. Joo-Hyun Seo(서주현)
   Associate Professor, Department of Bio and Fermentation Convergence Technology, Kookmin University

   EDUCATION &  EXPERIENCES
   단백질진화연구실

최근 5년, 2019~현재

- 2023

Kim, J. Y., Park, G.-G., Kim, E.-J., Park, B. S., Lee, J., Song, H., Park, B. G., Kazlauskas, R., Seo, J.-H. and Kim, B.-G. (2023). Identifying key residues in lysine decarboxylase for soluble expression using consensus design soluble mutant screening (ConsenSing). ACS Synth Biol accepted. Joo-Hyun Seo and Byung-Gee Kim are equally contributed corresponding authors.

Shin, J. and Seo, J.-H. (2023). Directed evolution of lipase to have enhanced activity toward short chain fatty acids and elucidation of structural features of mutant. KSBB J 38(1):21-27.

- 2022

Choi, J., Kim, E.-M., Ko, B. J., Lee, U.-J., Seo, J.-H. and Kim, B.-G. (2022). Production of theasinensin A using laccase as antioxidant and antiaging agent. Biotechnol Bioprocess Eng 27(2):253-261. Joo-Hyun Seo and Byung-Gee Kim are equally contributed corresponding authors.

Park, H., Seo, S. I., Lim, J.-H., Song, J., Seo, J.-H. and Kim, P. I. (2022). Screening of carbofuran-degrading bacteria Chryseobacterium sp. BSC2-3 and unveiling the change in metabolome during carbofuran degradation. Metabolites 12(3):219. Seo and Kim are equally contributed corresponding authors.

- 2020

Song, J.-W., Seo, J.-H., Oh. D.-K., Bornscheuer, U. T. and Park, J.-B. (2020). Design and engineering of whole-cell biocatalytic cascades for the valorization of fatty acids. Catal Sci Technol 10(1):46-64. Song and Seo are equally contributed first authors.

- 2019

Choi, Y. H., Park, B. S., Seo, J.-H. and Kim, B.-G. (2019). Biosynthesis of the human milk oligosaccharides 3-fucosyllactose in metabolically engineered Escherichia coli via the salvage pathway through increasing GTP synthesis and β-galactosidase modification. Biotechnol Bioeng, 116(12):3324-3332. Seo and Kim contributed equally as corresponding authors.

Jeon, J.-M., Choi, T.-R., Lee, B.-R., Seo, J.-H., Jung, H.-R., Yang, S.-Y., Park, J.-Y., Kim, E.-J., Kim, B.-G. and Yang, Y.-H. (2019). Decreased growth and antibiotic production in Streptomyces coelicolor A3(2) by deletion of a highly conserved DeoR family regulator, SCO1463. Biotechnol Bioprocess Eng, 24(4):613-621.

Upadhyay, R., Kim, J. Y., Hong, E. Y., Lee, S.-G., Seo, J.-H., Kim, B.-G. (2019). RiSLnet: rapid identification of smart mutant libraries using protein structure network. Application to thermal stability enhancement. Biotechnol Bioeng, 116(2):250-259. Joo-Hyun Seo and Byung-Gee Kim contributed equally as corresponding authors.

Kim, J. Y., Yoo, H.-W., Lee, P.-G., Lee, S.-G., Seo, J.-H., Kim, B.-G. (2019). In vitro protein evolution, next generation protein engineering strategy: from random approach to target-specific approach. Biotechnol Bioprocess Eng, 24(1):85-94. This article won 'The 2022 BBE Best Article Award'.

지도교수: 서주현 교수

 (2023년 현재)

 Post-doctoral researcher : 전강인

 Master Course : 김상래, 한성은, 박성수, 박민수

 Undergraduate: 김민하, 한승희

Contact : joohyunseo@kookmin.ac.kr

Homepage: http://pel.kookmin.ac.kr/index.html