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Structure-Based Gene Targeting Discovery of Sphaerimicin, a Bacterial Translocase I Inhibitor

Authors

  • Dr. Masanori Funabashi,

    1. Natural Product Research Group, Discovery Science and Technology Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd. Tokyo 134-8630 (Japan)
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  • Dr. Satoshi Baba,

    1. New Modality Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd. Tokyo 140-8710 (Japan)
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  • Dr. Toshio Takatsu,

    1. Analytical Chemistry Research Group, Center for Pharmaceutical and Biomedical Analysis, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630 (Japan)
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  • Masaaki Kizuka,

    1. Natural Product Research Group, Discovery Science and Technology Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd. Tokyo 134-8630 (Japan)
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  • Yasuo Ohata,

    1. Analytical Chemistry Research Group, Center for Pharmaceutical and Biomedical Analysis, Daiichi Sankyo RD Novare Co., Ltd., Tokyo 134-8630 (Japan)
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  • Dr. Masahiro Tanaka,

    1. Natural Product Research Group, Discovery Science and Technology Department, Drug Discovery and Biomedical Technology Unit, Daiichi Sankyo RD Novare Co., Ltd. Tokyo 134-8630 (Japan)
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  • Dr. Koichi Nonaka,

    1. Biologics Technology Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd. Gunma 370-0503 (Japan)
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  • Anatol P. Spork,

    1. Department of Chemistry, University of Paderborn, Paderborn 33098 (Germany)
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  • Prof. Dr. Christian Ducho,

    1. Department of Chemistry, University of Paderborn, Paderborn 33098 (Germany)
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  • Wei-Chen Leyla Chen,

    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40536 (USA)
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  • Prof. Dr. Steven G. Van Lanen

    Corresponding author
    1. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40536 (USA)
    • Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40536 (USA)

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  • This work was supported by NIH grant AI087849 to S.G.V.L.

Abstract

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Rise and shine: Using a gene-targeting approach aimed at identifying potential L-threonine:uridine-5′-transaldolases that catalyze the formation of (5′S,6′S)-C-glycyluridine, a new bacterial translocase I inhibitor was discovered from an actinomycete following fermentation optimization.

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