Won-Gon Kim

Korea Research Institute of Bioscience and Biotechnology KRIBB, Ansan, Gyeonggi, South Korea

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Publications (62)127.4 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 µM. It also prevented the growth of S. aureus and methicillin-resistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 µg·mL(-1). To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA.
    Biological & Pharmaceutical Bulletin 01/2014; 37(8):1406-10. · 1.85 Impact Factor
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    ABSTRACT: An highly quaternary and unprecedented dispiro compound, verrulactone C, with the known compound, altenuisol, were isolated from a culture broth of the fungal strain Penicillium verruculosum F375 and their structures were established by various spectral analysis. Verrulactone C and altenuisol showed FabI-selective inhibition. Especially altenuisol had the high correlation between FabI-inhibition and whole cell antibacterial activity against Staphylococcus aureus and MRSA with MICs of 8-32μg/mL.
    Bioorganic & medicinal chemistry letters 12/2013; · 2.65 Impact Factor
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    ABSTRACT: In the continued search for inhibitors of enoyl-acyl carrier protein (ACP) reductase, we found that four acylbenzenediol sulfate metabolites from Streptomyces sp. AN1761 potently inhibited bacterial enoyl-ACP reductases of Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. Their structures were identified as panosialins A, B, wA, and wB by MS and NMR data. They showed stronger inhibition against S. aureus FabI and S. pneumoniae FabK with IC50 of 3-5 microM than M. tuberculosis InhA with IC50 of 9-12 microM. They also exhibited a stronger antibacterial spectrum on S. aureus and S. pneumoniae than M. tuberculosis. In addition, the higher inhibitory activity of panosialin wB than panosialin B on fatty acid biosynthesis was consistent with that on bacterial growth, suggesting that they could exert their antibacterial activity by inhibiting fatty acid synthesis.
    Journal of Microbiology and Biotechnology 02/2013; 23(2):184-8. · 1.40 Impact Factor
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    ABSTRACT: Bacterial enoyl-acyl carrier protein reductase (FabI) is a promising novel antibacterial target. We isolated a new class of FabI inhibitor from Penicillium chrysogenum, which produces various antibiotics, the mechanisms of some of them are unknown. The isolated FabI inhibitor was determined to be meleagrin by mass spectroscopy and nuclear magnetic resonance spectral analyses, and its more active and inactive derivatives were chemically prepared. Consistent with their selective inhibition of Staphylococcus aureus FabI, meleagrin and its more active derivatives directly bound to S. aureus FabI in a fluorescence quenching assay, inhibited intracellular fatty acid biosynthesis and growth of S. aureus, and increased the minimum inhibitory concentration for fabI-overexpressing S. aureus. The compounds that were not effective against the FabK isoform, however, inhibited the growth of Streptococcus pneumoniae that contained only the FabK isoform. Additionally no resistant mutant to the compounds was obtained. Importantly, fabK-overexpressing Escherichia coli was not resistant to these compounds, but was resistant to triclosan. These results demonstrate that the compounds inhibited another target in addition to FabI. Thus, meleagrin is a new class of FabI inhibitor with at least one additional mode of action that could have potential for treating multidrug-resistant bacteria.
    PLoS ONE 01/2013; 8(11):e78922. · 3.73 Impact Factor
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    ABSTRACT: Flavimycins A (1) and B (2), novel dimeric 1,3-dihydroisobenzofurans, were isolated as inhibitors of peptide deformylase from cultures of Aspergillus flavipes. Their chemical structures were established by NMR and MS data analysis. Compounds 1 and 2 exist as epimeric mixtures at C-1 through fast hemiacetal-aldehyde tautomerism. Compounds 1 and 2 inhibited Staphylococcus aureus peptide deformylase with IC₅₀ values of 35.8 and 100.1 μM, respectively. Consistent with their PDF inhibition, 1 showed two times stronger antibacterial activity than 2 on S. aureus including MRSA, with MIC values of 32-64 μg/mL.
    Journal of Natural Products 02/2012; 75(2):271-4. · 3.29 Impact Factor
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    ABSTRACT: New dimeric compounds of alternariol class, verrulactones A and B, were isolated from a culture broth of the fungal strain Penicillium verruculosum F375 and their structure were established by various spectral analysis. Verrulactones A and B strongly inhibited Staphylococcus aureus enoyl-ACP reductase with IC(50) of 0.92 and 1.41 μM, respectively, and also showed antibacterial activity against S. aureus and MRSA with MICs of 8 and 16 μg/mL, respectively.
    Bioorganic & medicinal chemistry letters 02/2012; 22(7):2503-6. · 2.65 Impact Factor
  • Yu Jin Kim, Mi-Jin Sohn, Won-Gon Kim
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    ABSTRACT: Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In the screening of inhibitors of Staphylococcus aureus enoyl-ACP reductase (FabI), we found that a methanol extract of leaves of Morus alba L. potently inhibited S. aureus FabI as well as growth of S. aureus. The active principles were identified as chalcomoracin and moracin C by MS and NMR analysis. Chalcomoracin and moracin C inhibited S. aureus FabI with IC(50) of 5.5 and 83.8 µM, respectively. They also prevented the growth of S. aureus with minimum inhibitory concentration (MIC) of 4 and 32 µg/mL, respectively. Consistent with their inhibition against FabI and bacterial growth, they prevented (14)C]acetate incorporation into fatty acid in S. aureus while didn't affect protein synthesis. In this study, we reported that chalcomoracin and moracin C, potent antibacterial compounds from Morus alba, inhibited FabI and fatty acid synthesis.
    Biological & Pharmaceutical Bulletin 01/2012; 35(5):791-5. · 1.85 Impact Factor
  • Yun-Ju Kwon, Mi-Jin Sohn, Won-Gon Kim
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    ABSTRACT: antibacterial; aquastatin; enoyl-ACP reductase; Sporothrix; Staphylococcus aureus
    The Journal of Antibiotics 02/2011; 64(2):213-6. · 2.19 Impact Factor
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    ABSTRACT: A new trimeric hispidin derivative, phellinstatin, was isolated from a culture broth of the medicinal fungus Phellinus linteus and its structure was established by various spectral analysis. Phellinstatin strongly inhibited Staphylococcus aureus enoyl-ACP reductase with an IC(50) of 6 μM and also showed antibacterial activity against S. aureus and MRSA.
    Bioorganic & medicinal chemistry letters 01/2011; 21(6):1716-8. · 2.65 Impact Factor
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    ABSTRACT: Bacterial enoyl-ACP reductase (FabI) has been demonstrated to be a novel antibacterial target. In the course of our screening for FabI inhibitors we isolated two methyl-branched fatty acids from Streptomyces sp. A251. They were identified as 14-methyl-9(Z)-pentadecenoic acid and 15-methyl-9(Z)-hexadecenoic acid by MS and NMR spectral data. These compounds inhibited Staphylococcus aureus FabI with IC50 of 16.0 and 16.3mu M, respectively, while didn't affect FabK, an enoyl-ACP reductase of Streptococcus pneumonia, at 100muM. Consistent with their selective inhibition for FabI, they blocked intracellular fatty acid synthesis as well as the growth of S. aureus, while didn't inhibit the growth of S. pneumonia. Additionally, these compounds showed reduced antibacterial activity against fabI-overexpressing S. aureus compared to the wild-type strain. These results demonstrate that the methyl-branched fatty acids showed antibacterial activity by inhibiting FabI in vivo.
    Journal of Microbiology and Biotechnology 05/2010; 20(5):875-80. · 1.40 Impact Factor
  • Chang-Ji Zheng, Hyun-Woo Oh, Won-Gon Kim
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    ABSTRACT: Aceriphyllum rossii Engler (Saxifragaceae) have been used as a nutritious food in Korea. We found that the methanol extract of A. rossii root and its components, aceriphyllic acid A and 3-oxoolean-12-en-27-oic acid, potently inhibited the growth of the key cariogenic bacteria, Streptococcus mutans, with MIC of 2 to 4 microg/mL. They also showed antibacterial activity against other cariogenic bacteria such as S. oralis, S. sobrinus, and S. salivarius with the similar potency. In the time-kill study, aceriphyllic acid A reduced the viable counts of S. mutans by 90% in 1 min at 8 microg/mL, indicating that aceriphyllic acid A had the fast bacteriostatic activity. Severe damages of the cell surface of S. mutans by aceriphyllic acid A were observed by transmission electron microscopy, suggesting with its fast antibacterial activity that its mechanism of action might be membrane disruption. These results suggest that the methanol extract of A. rossii root and its components, aceriphyllic acid A and 3-oxoolean-12-en-27-oic acid, could have the great potential as natural agents for preventing dental caries.
    Journal of Food Science 03/2010; 75(2):M78-82. · 1.78 Impact Factor
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    Yun-Ju Kwon, Chang-Ji Zheng, Won-Gon Kim
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    ABSTRACT: Two highly hydroxylated 1,3-dihydroisobenzofurans, FR198248 (1) and FR202306 (2), were isolated as peptide deformylase (PDF) inhibitors from Aspergillus flavipes. Compounds 1 and 2 inhibited Staphylococus aureus PDF with IC(50) values of 3.6 and 2.5 microM, respectively, and also showed antibacterial activity with an MIC value of 25 microg/ml. In contrast, 6-O-methyl derivative 3 of compound 2 was inactive against both PDF and S. aureus.
    Bioscience Biotechnology and Biochemistry 02/2010; 74(2):390-3. · 1.27 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 31(3).
  • Won-Gon Kim, Nan-Kyu Song, Ick-Dong Yoo
    ChemInform 01/2010; 33(33).
  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 33(33).
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    ABSTRACT: Rhus trichocarpa Miquel has been utilised both as a food and for medicinal purposes. In this study, we determined that the methanol extracts of the stem and leaf portions of R. trichocarpa inhibited the growth of both Gram-negative and Gram-positive bacteria. The active constituent was isolated, and identified via mass spectrometry and NMR as 1,2,3,4,6-penta-O-galloyl-β-d-glucose. The compound also evidenced a broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria including Staphylococcus aureus (both methicillin-resistant S. aureus and quinolone-resistant S. aureus), Bacillus subtilis, Streptococcus mutans, Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa with MRC values of 16–32μg/ml, whereas gallate failed to inhibit the growth of Gram-negative bacteria, even at a concentration of 128μg/ml. The antibacterial activity of penta-O-galloylglucose was restored by the addition of Fe2+, whereas gallate was not, thereby indicating that its antibacterial activity could be attributable to the chelation of iron. The results of the time-kill study against S. aureus and E. coli revealed that penta-O-galloylglucose exhibited bacteriostatic activity. These findings indicate that the extracts of R. trichocarpa as well as its active component, penta-O-galloylglucose, may have profound potential for the control of both Gram-positive and negative pathogens.
    Food Chemistry - FOOD CHEM. 01/2010; 123(2):501-506.
  • Won-Gon Kim, Nan-Kyu Song, Ick-Dong Yoo
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 33(15).
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    ABSTRACT: Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Sporothrix sp. FN611 potently inhibited the enoyl-ACP reductase (FabI) of Staphylococcus aureus. Its structure identified the metabolite as aquastatin A by the MS and NMR data. Aquastatin A inhibited S. aureus FabI with an IC(50) of 3.2 microM. It also prevented the growth of S. aureus and methicillin-resistant Staphylococcus aureus (MRSA) with minimum inhibitory concentration of 16-32 microg/ml. Aquastatin A also exerted an inhibitory effect against the FabK isoform, an enoyl-ACP reductase of Streptococcus pneumoniae, with an IC(50) of 9.2 microM. The degalactosylation of aquastatin A did not affect the FabI and FabK-inhibitory or antibacterial activities, thereby suggesting that the sugar moiety within its molecular structure was not involved in these activities. The inhibitory effects of aquastatin A and its degalactosylated derivative on enoyl-ACP reductases and bacterial viability are reported for the first time in this study; these effects point to the potential that aquastatin A may be developed into a new broad-spectrum antibacterial and anti-MRSA agent.
    Biological & Pharmaceutical Bulletin 12/2009; 32(12):2061-4. · 1.85 Impact Factor
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    ABSTRACT: Previously, we reported that a fungal metabolite, terrein, decreases melanin synthesis via downregulation of microphthalmia-associated transcription factor (MITF). In the present study, we further investigated the long-term hypopigmenting action of terrein in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment with terrein at a concentration of 50 mum strongly decreased melanogenesis in a time-dependent manner. Interestingly, the decreased tyrosinase protein levels lasted for at least 7 days, even though the MITF protein levels were restored after 3 days of treatment. In accordance with the results of Western blot analyses, the tyrosinase mRNA levels were found to be continuously decreased for at least 7 days, even though recovery of the MITF mRNA levels began after 3 days of terrein treatment. Therefore, we evaluated tyrosinase downregulation to determine if it is caused by proteasomal degradation. We found that the reduction in tyrosinase levels that was induced by terrein was clearly recovered by MG-132, a proteasome inhibitor. Moreover, ubiquitination of tyrosinase increased following treatment with terrein in the presence of MG-132. Taken together, these results suggest that terrein decreases melanogenesis through ubiquitin-dependent proteasomal degradation as well as via decreased expression of its mRNA.
    Experimental Dermatology 07/2009; 18(6):562-6. · 3.58 Impact Factor
  • Chang Ji Zheng, Mi-Jin Sohn, Won-Gon Kim
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    ABSTRACT: Bacterial enoyl-ACP reductase (FabI) has been validated as a novel antibacterial target for tackling infections caused by multidrug-resistant pathogens. A few FabI inhibitors, however, are known. This study isolated a new FabI inhibitor from Penicillium sp. A screening programme led to the selection of a Penicillium sp. producing a strong FabI-inhibitory metabolite. The chemical structure of the isolated FabI inhibitor was elucidated by mass spectrometry and nuclear magnetic resonance spectral data. The antibacterial target of the inhibitor was validated by overexpression assays. The isolated FabI inhibitor was elucidated to be vinaxanthone. It selectively inhibited Staphylococcus aureus FabI with an IC(50) of 0.9 microM; it did not affect FabK, an enoyl-ACP reductase of Streptococcus pneumoniae. Consistent with its inhibition of FabI, the inhibitor prevented intracellular fatty acid synthesis while it did not affect protein biosynthesis. It also prevented the growth of S. aureus as well as methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus. Importantly, fabI-overexpressing S. aureus showed reduced susceptibility to the inhibitor compared with the wild-type strain, demonstrating that its antibacterial action is mediated by inhibition of FabI. Vinaxanthone is a new FabI-directed antibacterial of natural origin that could have potential for further development as a new anti-MRSA agent.
    Journal of Antimicrobial Chemotherapy 06/2009; 63(5):949-53. · 5.34 Impact Factor

Publication Stats

326 Citations
127.40 Total Impact Points

Institutions

  • 1996–2013
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • • Environmental Biotechnology Research Center
      • • Functional Metabolite Research Center
      Ansan, Gyeonggi, South Korea
  • 2010
    • Yanbian University
      Yang-chi-t'eng, Jilin Sheng, China
  • 2007
    • Korea Research Institute of Chemical Technology
      Daiden, Daejeon, South Korea