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Research Area
Site-specific Protein Modification

"Marking-Activation-Coupling" approach to attach various functional groups to the protein
Site-specific, authentic protein modification
Genetic Incorporation of
Non-canonical Amino Acids into Proteins

Development of new methods for the incorporation of ncAAs into proteins
Design and engineering of translational machineries for the genetic code expansion
Phosphoserine Incorporation

Structural biology of phosphoproteins
Detailed mapping of protein kinase signaling networks
Anti-cancer drug design based on activated target-ligand structures
High-throughput screening of kinase inhibitors
Protein Engineering and Directed Evolution

Rational design of enzymes based on structural analysis
Molecular evolution of proteins for the enhanced properties
Hee-Sung Park
λ°ν¬μ±
2022~ Professor
Dept. of Chemistry, KAIST
2013-2022 Associate Professor
Dept. of Chemistry, KAIST
2009-2013 Assistant Professor
Dept. of Chemistry, KAIST
2008-2009 Research Faculty
Dept. of Molecular Biophysics & Biochemistry,
Yale University
2005-2008 Postdoctoral Associate
under Prof. Dieter SΓΆll
at Dept. of Molecular Biophysics & Biochemistry,
Yale University
2000-2005 Postdoctoral Associate
under Prof. Hak-Sung Kim
at Dept. of Biological Sciences, KAIST
2000 Ph.D. in Chemical Engineering, KAIST
1996 M.S. in Biological Sciences, KAIST
1994 B.S. in Food Science and Biotechnology,
Seoul National University

Current Members
Alumni

SangSik Lee
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Ph.D.

JiHyo Kim
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Ph.D.

KyoungHwa Woo
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M.S.

Aerin Yang
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Ph.D.

KyuKwang Cho
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Ph.D.

KyungJin Lee
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Ph.D.

OkMin Kim
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M.S.

Juhyeon Kim
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M.S.

DongHyuk Gang
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Ph.D.

YunSu Kim
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M.S.

DeokHee Kang
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Ph.D.

DoWook Kim
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Ph.D.

SuHo Cho
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Joo-Chan Kim
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Ph.D.
Site-specific Protein Modification

Phosphoserine Incorporation
Science, 333(6046):1151-1154. (2011)
Angew. Chem. Intl. Ed., 52(22):5771-5775. (2013)

Acetyllysine Incorporation
Nat. Commun., 8:14568. (2017)
FEBS Lett., 586(6):729-733. (2012)

Drug Screening Platform
Angew. Chem. Intl. Ed., 62(7):e202214815. (2023)
Chem. Commun., 52:12112-12115. (2016)

β : these authors have contributed to the work equally.
* : corresponding author
2024
Joo-Chan Kim, YouJin Kim, Suho Cho, and Hee-Sung Park*
Noncanonical Amino Acid Incorporation in Animals and Animal Cells
Chemical Reviews, Nov 2024; 124(22): 12463-12497.
DOI:10.1021/acs.chemrev.3c00955
Kwangbeom Hyun, Jihye Ahn, Hyoungmin Kim, Jihyun Kim, Yong-In Kim, Hee-Sung Park, Robert G. Roeder, J. Eugene Lee*, and Jaehoon Kim*
The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain
Nature Communications, Nov 2024; 15(1): 9614.
DOI:10.1038/s41467-024-53981-0
YouJin Kimβ , Suho Choβ , Joo-Chan Kim, and Hee-Sung Park*
tRNA Engineering Strategies for Genetic Code Expansion
Frontiers in Genetics, Mar 2024; 15: 1373250.
DOI: 10.3389/fgene.2024.1373250
2023
Marcel Janis Behaβ , Joo-Chan Kimβ , San Hae Imβ , Yunsu Kim, Seungju Yang, Juhee Lee, Yu Ri Nam, Haeshin Lee, Hee-Sung Park*, and Hyun Jung Chung*
Bioorthogonal CRISPR/Cas9-Drug Conjugate: A Combinatorial Nanomedicine Platform
Advanced Science, Sep 2023; 10(27):2302253.
DOI: 10.1002/advs.202302253
Neha Jainβ , Prasad M. Sonawaneβ , Haoyan Liu, Arkaprava Roychaudhury, Youngseob Lee, Jongkeol An, Donghyeon Kim, Dongwook Kim, Yunsu Kim, Yeu-Chun Kim, Kyung-Bin Cho, Hee-Sung Park, Cheol-Hee Kim*, and David G. Churchill*
"Lighting Up" Fluoride: Cellular Imaging and Zebrafish Model Interrogations using a Simple ESIPT-based Mycophenolic Acid Precursor-based Probe
Analyst, May 2023; 148:2609-2615.
DOI: 10.1039/D3AN00646H
Deokhee Kangβ , Do-Wook Kimβ , Joo-Chan Kim, and Hee-Sung Park*
A Versatile Strategy for Screening Custom-Designed Warhead-Armed Cyclic Peptide Inhibitors
Angewandte Chemie International Edition, Feb 2023; 62(7):e202214815.
DOI: 10.1002/anie.202214815
2022
Seonghoon Kim, Hee-Sung Park, and Byung-Ha Oh*
Computational Design of an Apoptogenic Protein that Binds BCL-xL and MCL-1 Simultaneously and Potently
Computational and Structural Biotechnology Journal, Jun 2022; 20:3019-3029.
DOI: 10.1016/j.csbj.2022.06.021
Prasad M. Sonawane, Woohyun Lee, Yunsu Kim, Arkaprava Roychaudhury, Vikas K. Bhosale, Donghyeon Kim, Hee-Sung Park, Cheol-Hee Kim*, and David G. Churchill*
Phosphinate-benzoindocyanin Fluorescent Probe for Endogenous Mitochondrial Peroxynitrite Detection in Living Cells and Gallbladder Access in Inflammatory Zebrafish Animal Models
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Feb 2022; 267(2):120568.
DOI: 10.1016/j.saa.2021.120568
2021
Prasad M. Sonawane, Tesla Yudhistira, Mahesh B. Halle, Arkaprava Roychaudhury, Yunsu Kim, Sachin S. Surwase, Vikas K. Bhosale, Juhyeon Kim, Hee-Sung Park, Yeu-chun Kim, Cheol-Hee Kim*, and David G. Churchill*
A Water-soluble Boronate masked Benzoindocyanin Fluorescent Probe for the Detection of Endogenous Mitochondrial Peroxynitrite in Live Cells and Zebrafish as Inflammation Models
Dyes and Pigments, Jul 2021; 191:109371.
DOI: 10.1016/j.dyepig.2021.109371
Donghyeok Gang and Hee-Sung Park*
Noncanonical Amino Acids in Synthetic Biosafety and Post-translational Modification Studies
ChemBioChem, Feb 2021; 22(3):460-468.
DOI: 10.1002/cbic.202000437
2020
Phuong Thi Mai Duong, Anh Thi Ngoc Bui, Seong-Ok Kim, Hee-Sung Park*, Yeon-Soo Seo, and Byong-Seok Choi*
The Interaction between Ubiquitin and Yeast Polymerase Ξ· C-terminus Does Not Require the UBZ Domain
FEBS Letters, Jun 2020; 594(11):1726-1737.
DOI: 10.1002/1873-3468.13783
2019
Ina Yoon, Miso Nam, Hoi Kyoung Kim, Hee-Sun Moon, Sungmin Kim, Jayun Jang, Ji Ae Song, Seung Jae Jeong, Sang Bum Kim, Seongmin Cho, Younha Kim, Jihye Lee, Won Suk Yang, Hee Chan Yoo, Kibum Kim, Min-Sun Kim, Aerin Yang, Kyukwang Cho, Hee-Sung Park, Geum-Sook Hwang, Kwang Yeon Hwang, Jung Min Han, Jong Hyun Kim*, and Sunghoon Kim*
Glucose-dependent Control of Leucine Metabolism by Leucyl-tRNA Synthetase 1
Science, Nov 2019; 367(6474):205-210.
DOI: 10.1126/science.aau2753
Kyung Jin Lee, Deokhee Kang, and Hee-Sung Park*
Site-Specific Labeling of Proteins Using Unnatural Amino Acids
Molecules and Cells, May 2019; 42(5):386-396.
DOI: 10.14348/molcells.2019.0078
2018
Mahesh B. Halle, Kyung Jin Lee, Tesla Yudhistira, Jae Hyuck Choi, Hee-Sung Park, and David G. Churchill*
A Hemicyanine-Embedded Diphenylselenide-Containing Probe "HemiSe" in which SePh2 Stays Reduced for Selective Detection of Superoxide in Living Cells
Chemistry - An Asian Journal, Dec 2018; 13(24):3895-3902.
DOI: 10.1002/asia.201801339
Donghyeok Gang, Do Wook Kim, and Hee-Sung Park*
Cyclic Peptides: Promising Scaffolds for Biopharmaceuticals
Genes, Nov 2018; 9(11):557.
DOI: 10.3390/genes9110557
Mahesh B. Halle, Tesla Yudhistira, Kyung Jin Lee, Jae Hyuck Choi, Youngsam Kim, Hee-Sung Park, and David G. Churchill*
Overriding Phthalate Decomposition When Exploring Mycophenolic Acid Intermediates as Selenium-Based ROS Biological Probes
ACS Omega, Oct 2018; 3(10):13474-13483.
DOI: 10.1021/acsomega.8b01571
Jihye Ahn, Jin Gyeong Lee, Chuevin Chin, Suna In, Aerin Yang, Hee-Sung Park, Jaehoon Kim*, and Jeong Hyeon Park*
MSK1 Functions as a Transcriptional Coactivator of p53 in the Regulation of p21 Gene Expression
Experimental and Molecular Medicine, Oct 2018; 50:1-12.
DOI: 10.1038/s12276-018-0160-8
Hyunhee Kim, Hyelim Jo, Hogyu David Seo, Hee-Sung Park, and Daeyoup Lee*
Chd1p Recognizes H3K36Ac to Maintain Nucleosome Positioning Near the Transcription Start Site
Biochemical and Biophysical Research Communications, Sep 2018; 503(3):1200-1206.
DOI: 10.1016/j.bbrc.2018.07.025
Samira Husen Alamudiβ , Dongdong Suβ , Kyung Jin Lee, Jung Yeol Lee, JosΓ© Luis Belmonte-VΓ‘zquez, Hee-Sung Park, Eduardo PeΓ±a-Cabrera*, and Young-Tae Chang*
A Palette of Background-Free Tame Fluorescent Probes for Intracellular Multi-color Labelling in Live Cells
Chemical Science, Jan 2018; 9:2376-2383.
DOI: 10.1039/C7SC04716A
2017
Sang-Woo Kim, Kyung Jin Lee, Sinil Kim, Jihyo Kim, Kyukwang Cho, Hyeon-Su Ro*, and Hee-Sung Park*
Genetic Incorporation of NΞ΅-Acetyllysine Reveals a Novel Acetylation-SUMOylation Switch in Yeast
Biochimica et Biophysica Acta (BBA) - General Subjects, Nov 2017; 1861(11B):3030-3037.
DOI: 10.1016/j.bbagen.2017.02.002
Siyeong Yang, Hongki Kim, Kyung Jin Lee, Seul Gee Hwang, Eun-Kyung Lim, Juyeon Jung, Tae Jae Lee, Hee-Sung Park*, Taejoon Kang*, and Bongsoo Kim*
Attomolar Detection of Extracellular microRNAs Released from Living Prostate Cancer Cells by a Plasmonic Nanowire Interstice Sensor
Nanoscale, Oct 2017; 9:17387-17395.
DOI: 10.1039/C7NR04386D
Aerin Yang, Kyukwang Cho, and Hee-Sung Park*
Chemical Biology Approaches for Studying Posttranslational Modifications
RNA Biology, Sep 2017; 15(4-5):427-440.
DOI: 10.1080/15476286.2017.1360468
Sandip V. Mulay, Youngsam Kim, Kyung Jin Lee, Tesla Yudhistira, Hee-Sung Park, and David G. Churchill*
A Fluorogenic and Red-shifted Diphenyl Phosphinate-based Probe for Selective Peroxynitrite Detection as Demonstrated in Fixed Cells
New Journal of Chemistry, Sep 2017; 41:11934-11940.
DOI: 10.1039/C7NJ02530K
Tesla Yudhistira, Sandip V. Mulay, Kyung Jin Lee, Youngsam Kim, Hee-Sung Park, and David G. Churchill*
Thiomaleimide Functionalization for Selective Biological Fluorescence Detection of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells
Chemistry - An Asian Journal, Aug 2017; 12(15):1927-1934.
DOI: 10.1002/asia.201700527
Songmi Han, Aerin Yang, Soonjang Lee, Han-Woong Lee, Chan Bae Park*, and Hee-Sung Park*
Expanding the Genetic Code of Mus musculus
Nature Communications, Feb 2017; 8:14568.
DOI: 10.1038/ncomms14568
2016
Steven Z. Josefowicz*, Miho Shimada, Anja Armache, Charles H. Li, Rand M. Miller, Shu Lin, Aerin Yang, Brian D. Dill, Henrik Molina, Hee-Sung Park, Benjamin A. Garcia, Jack Taunton, Robert G. Roeder*, and C. David Allis*
Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription
Molecular Cell, Oct 2016; 64(2):347-361.
DOI: 10.1016/j.molcel.2016.09.026
Aerin Yang, Sura Ha, Jihye Ahn, Rira Kim, Sungyoon Kim, Younghoon Lee, Jaehoon Kim, Dieter SΓΆll*, Hee-Yoon Lee*, and Hee-Sung Park*
A Chemical Biology Route to Site-Specific Authentic Protein Modifications
Science, Sep 2016; 354(6312):623-626.
DOI: 10.1126/science.aah4428
Jieon Lee, Il-Soo Park, Ginam Park, Kyukwang Cho, Hee-Sung Park, and Del-Hee Min*
A Robust and Quantitative Assay Platform for Multiplexed, High Throughput Screening of Protein Kinase Inhibitors
Chemical Communications, Sep 2016; 52:12112-12115.
DOI: 10.1039/C6CC05834E
Euihan Jung, Seonghui Jang, Jungmin Lee, Youngmi Kim, Heegwon Shin, Hee-Sung Park, and Younghoon Lee*
Truncated SRA RNA Derivatives Inhibit Estrogen Receptor-Ξ±-mediated Transcription
Molecular Biology Reports, Jul 2016; 43:1019-1025.
DOI: 10.1007/s11033-016-4039-2
Samira Husen Alamudi, Rudrakanta Satapathy, Jihyo Kim, Dongdong Su, Haiyan Ren, Rajkumar Das, Lingna Hu, Enrique Alvarado-MartΓnez, Jung Yeol Lee, Christian Hoppmann, Eduardo PeΓ±a-Cabrera, Hyung-Ho Ha, Hee-Sung Park*, Lei Wang* and Young-Tae Chang*
Development of Background-Free Tame Fluorescent Probes for Intracellular Live Cell Imaging
Nature Communications, Jun 2016; 7:11964.
DOI: 10.1038/ncomms11964
2015
Gil Ju Seo, Aerin Yang, Brandon Tan, Sungyoon Kim, Qiming Liang, Younho Choi, Weiming Yuan, Pinghui Feng, Hee-Sung Park, and Jae U. Jung*
Akt Kinase-Mediated Checkpoint of cGAS DNA Sensing Pathway
Cell Reports, Oct 2015; 13(2):440-449.
DOI: 10.1016/j.celrep.2015.09.007
2014
Mude Shi, Hyelim Cho, Kyung-Soo Inn, Aerin Yang, Zhen Zhao, Qiming Liang, Gijs A. Versteeg, Samad Amini-Bavil-Olyaee, Lai-Yee Wong, Berislav V. Zlokovic, Hee-Sung Park, Adolfo GarcΓa-Sastre, and Jae U. Jung*
Negative Regulation of NF-ΞΊB Activity by Brain-specific TRIpartite Motif protein 9
Nature Communications, Sep 2014; 5:4820.
DOI: 10.1038/ncomms5820
Yonghwang Ha, Aerin Yang, Seyoung Lee, Kibong Kim, Hyunjeong Liew, Sang Hyung Lee, Ju Eun Lee, Hong-In Lee, Yoo-Hun Suh*, Hee-Sung Park*, and David G. Churchill*
Dopamine and Cu+/2+ Can Induce Oligomerization of Ξ±-Synuclein in the Absence of Oxygen: Two Types of Oligomerization Mechanisms for Ξ±-Synuclein and Related Cell Toxicity Studies
Journal of Neuroscience Research, Mar 2014; 92(3):359-368.
DOI: 10.1002/jnr.23323
Yonghwang Ha, Aerin Yang, Seyoung Lee, Kibong Kim, Hyunjeong Liew, Yoo-Hun Suh*, Hee-Sung Park*, and David G. Churchill*
Facile "Stop Codon" Method Reveals Elevated Neuronal Toxicity by Discrete S87p-Ξ±-Synuclein Oligomers
Biochemical and Biophysical Research Communications, Jan 2014; 443(3):1085-1091.
DOI: 10.1016/j.bbrc.2013.12.099
2013
Sangsik Lee, Seunghee Oh, Aerin Yang, Jihyo Kim, Dieter SΓΆll, Daeyoup Lee*, and Hee-Sung Park*
A Facile Strategy for Selective Incorporation of Phosphoserine into Histones
Angewandte Chemie International Edition, May 2013; 52(22):5771-5775.
[Selected as V.I.P. and Front Cover]
DOI: 10.1002/anie.201300531
2012
Jihyo Kim, Moon-Hyeong Seo, Sangsik Lee, Kyukwang Cho, Aerin Yang, Kyunghwa Woo, Hak-Sung Kim*, and Hee-Sung Park*
Simple and Efficient Strategy for Site-Specific Dual Labeling of Proteins for Single-Molecule Fluorescence Resonance Energy Transfer Analysis
Analytical Chemistry, Dec 2012; 85(3):1468-1474.
DOI: 10.1021/ac303089v
Takuya Umehara, Jihyo Kim, Sangsik Lee, Li-Tao Guo, Dieter SΓΆll*, and Hee-Sung Park*
N-Acetyl Lysyl-tRNA Synthetases Evolved by a CcdB-based Selection Possess N-Acetyl Lysine Specificity in vitro and in vivo
FEBS Letters, Mar 2012; 586(6):729-733.
DOI: 10.1016/j.febslet.2012.01.029
2011
Moon-Hyeong Seo, Tae-Sun Lee, Eunkyung Kim, Young Lag Cho, Hee-Sung Park, Tae-Young Yoon*, and Hak-Sung Kim*
Efficient Single-Molecule Fluorescence Resonance Energy Transfer Analysis by Site-Specific Dual-Labeling of Protein Using an Unnatural Amino Acid
Analytical Chemistry, Oct 2011; 83(23):8849-8854.
DOI: 10.1021/ac202096t
Hee-Sung Parkβ , Michael J. Hohnβ , Takuya Umehara, Li-Tao Guo, Edith M. Osborne, Jack Benner, Christopher J. Noren*, Jesse Rinehart*, and Dieter SΓΆll*
Expanding the Genetic Code of Escherichia coli with Phosphoserine
Science, Aug 2011; 333(6046):1151-1154.
DOI: 10.1126/science.1207203
Moon-Hyeong Seo, Jieun Han, Zongwen Jin, Dong-Won Lee, Hee-Sung Park*, and Hak-Sung Kim*
Controlled and Oriented Immobilization of Protein by Site-Specific Incorporation of Unnatural Amino Acid
Analytical Chemistry, Mar 2011; 83(8):2841-2845.
DOI: 10.1021/ac103334b
2007
Satwik Kamtekar, Michael J. Hohn, Hee-Sung Park, Michael Schnitzbauer, Anselm Sauerwald, Dieter SΓΆll, and Thomas A. Steitz*
Toward Understanding Phophoseryl-tRNACys Formation: The Crystal Structure of Methanococcus maripaludis Phosphoseryl-tRNA Synthetase
Proceedings of the National Academy of Sciences, Feb 2007; 104(8):2620-2625.
DOI: 10.1073/pnas.0611504104
2006
Michael J. Hohn, Hee-Sung Park, Patrick OβDonoghue, Michael Schnitzbauer, and Dieter SΓΆll*
Emergence of the Universal Genetic Code Imprinted in an RNA Record
Proceedings of the National Academy of Sciences, Nov 2006; 103(48):18095-18100.
DOI: 10.1073/pnas.0608762103
Hee-Sung Park, Sung-Hun Nam, Jin Kak Lee, Chang No Yoon, Bengt Mannervik, Stephen J. Benkovic, and Hak-Sung Kim*
Design and Evolution of New Catalytic Activity with an Existing Protein Scaffold
Science, Jan 2006; 311(5760):535-538.
DOI: 10.1126/science.1118953
2005
Sung-Hun Nam, Hee-Sung Park, and Hak-Sung Kim*
Evolutionary Relationship and Application of a Superfamily of Cyclic Amidohydrolase Enzymes
The Chemical Record, Oct 2005; 5(5):298-307.
DOI: 10.1002/tcr.20057
2004
Hee-Sung Park, Ki-Hoon Oh, and Hak-Sung Kim*
Improving the Functional Expression of N-Carbamoylase by Directed Evolution using the Green Fluorescent Protein Fusion Reporter System
Methods in Enzymology, Aug 2004; 388:187-195.
DOI: 10.1016/S0076-6879(04)88017-0
Young-Hoon Cheon, Hee-Sung Park, Jin-Hyun Kim and Hak-Sung Kim*
Manipulation of the Active Site Loops of D-Hydantoinase, a (Ξ²/Ξ±)8-Barrel Protein, for Modulation of the Substrate Specificity
Biochemistry, May 2004; 43(23):7413-7420.
DOI: 10.1021/bi036330o
2003
Young-Hoon Cheon, Hee-Sung Park, Sang-Chul Lee, Dong-Eun Lee, and Hak-Sung Kim*
Structure-based Mutational Analysis of the Active Site Residues of D-Hydantoinase
Journal of Molecular Catalysis B: Enzymatic, Dec 2003; 26(3-6):217-222.
DOI: 10.1016/j.molcatb.2003.06.005
2001
Hee-Sung Park, and Hak-Sung Kim*
Genetic and Structural Organization of the Aminophenol Catabolic Operon and Its Implication for Evolutionary Process
Journal of Bacteriology, Sep 2001; 183(17):5074-5081.
DOI: 10.1128/jb.183.17.5074-5081.2001
Geun-Joong Kim, Young-Hoon Cheon, Min-Soon Park, Hee-Sung Park, and Hak-Sung Kim*
Generation of Protein Lineages with New Sequence Spaces by Functional Salvage Screen
Protein Engineering, Design and Selection, Sep 2001; 14(9):647-654.
DOI: 10.1093/protein/14.9.647
2000
Hee-Sung Park and Hak-Sung Kim*
Identification and Characterization of the Nitrobenzene Catabolic Plasmids pNB1 and pNB2 in Pseudomonas putida HS12
Journal of Bacteriology, Feb 2000; 182(3):573-580.
DOI: 10.1128/jb.182.3.573-580.2000
1999
Jang-Young Lee, Hee-Sung Park, and Hak-Sung Kim*
Adenosylcobalamin-Mediated Methyl Transfer by Toluate cis-Dihydrodiol Dehydrogenase of the TOL Plasmid pWW0
Journal of Bacteriology, May 1999; 181(9):2953-2957.
DOI: 10.1128/jb.181.9.2953-2957.1999
Hee-Sung Park, Sung-Jin Lim, Yong Keun Chang, Andrew G. Livingston, and Hak-Sung Kim*
Degradation of Chloronitrobenzenes by a Coculture of Pseudomonas putida and a Rhodococcus sp
Applied and Environmental Microbiology, Mar 1999; 65(3):1083-1091.
DOI: 10.1128/AEM.65.3.1083-1091.1999
1998
Hee-Sung Park, Jang-Young Lee, and Hak-Sung Kim*
Production of L-DOPA(3,4-Dihydroxyphenyl-L-Alanine) from Benzene by Using a Hybrid Pathway
Biotechnology and Bioengineering, Apr 1998; 58(2-3):339-343.
DOI: 10.1002/(SICI)1097-0290(19980420)58:2/3<339::AID-BIT36>3.0.CO;2-4
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λμ κ΄μμ μ μ±κ΅¬ λνλ‘ 291 (ꡬμ±λ) νκ΅κ³ΌνκΈ°μ μ κΈ°μ΄κ³Όνλ (E6-6) 519νΈ