Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471

Zheng Cui; Xiachang Wang; Stefan Koppermann; Jon S. Thorson; Christian Ducho; Steven G. Van Lanen

doi:10.1021/acs.jnatprod.7b01054

Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471

Zheng Cui, Xiachang Wang, Stefan Koppermann, Jon S. Thorson, Christian Ducho, Steven G. Van Lanen

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC₅₀ values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 μg/mL, respectively) and Escherichia coli ΔtolC (MIC = 4 and 2 μg/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance.

Original language	English
Pages (from-to)	942-948
Number of pages	7
Journal	Journal of Natural Products
Volume	81
Issue number	4
DOIs	https://doi.org/10.1021/acs.jnatprod.7b01054
State	Published - Apr 27 2018

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants R01 AI087849 (S.V.L.), R01 GM115261 (J.S.T.), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, the National Center for Advancing Translational Sciences (UL1TR001998), and the Deutsche Forschungsgemeinschaft (DFG, grant DU 1095/5-1). NMR (600 MHz) data were collected at the NMR facility of the Center for Environmental Systems Biochemistry supported in part by 1U24DK097215-01A.

Publisher Copyright:
© 2018 American Chemical Society and American Society of Pharmacognosy.

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

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10.1021/acs.jnatprod.7b01054

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title = "Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471",

abstract = "Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC50 values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 μg/mL, respectively) and Escherichia coli ΔtolC (MIC = 4 and 2 μg/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance.",

author = "Zheng Cui and Xiachang Wang and Stefan Koppermann and Thorson, {Jon S.} and Christian Ducho and {Van Lanen}, {Steven G.}",

note = "Funding Information: This work was supported by National Institutes of Health grants R01 AI087849 (S.V.L.), R01 GM115261 (J.S.T.), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, the National Center for Advancing Translational Sciences (UL1TR001998), and the Deutsche Forschungsgemeinschaft (DFG, grant DU 1095/5-1). NMR (600 MHz) data were collected at the NMR facility of the Center for Environmental Systems Biochemistry supported in part by 1U24DK097215-01A. Publisher Copyright: {\textcopyright} 2018 American Chemical Society and American Society of Pharmacognosy.",

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AU - Van Lanen, Steven G.

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N2 - Muraymycins are nucleoside antibiotics isolated from Streptomyces sp. NRRL 30471 and several mutant strains thereof that were generated by random, chemical mutagenesis. Reinvestigation of two mutant strains using new media conditions led to the isolation of three new muraymycin congeners, named B8, B9, and C6 (1-3), as well as a known muraymycin, C1. Structures of the compounds were elucidated by HRMS and 1D and 2D NMR spectroscopic analyses. Complete 2D NMR assignments for the known muraymycin C1 are also provided for the first time. Compounds 1 and 2, which differ from other muraymycins by having an elongated, terminally branched fatty acid side chain, had picomolar IC50 values against Staphylococcus aureus and Aquifex aeolicus MraY and showed good antibacterial activity against S. aureus (MIC = 2 and 6 μg/mL, respectively) and Escherichia coli ΔtolC (MIC = 4 and 2 μg/mL, respectively). Compound 3, which is characterized by an N-acetyl modification of the primary amine of the dissacharide core that is shared among nearly all of the reported muraymycin congeners, greatly reduced its inhibitory and antibacterial activity compared to nonacylated muraymycin C1, which possibly indicates this modification is used for self-resistance.

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Antibacterial Muraymycins from Mutant Strains of Streptomyces sp. NRRL 30471

Abstract

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