IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-35227-z.html
   My bibliography  Save this article

Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY

Author

Listed:
  • Takeshi Nakaya

    (Hokkaido University)

  • Miyuki Yabe

    (Hokkaido University)

  • Ellene H. Mashalidis

    (Duke University School of Medicine
    Pfizer Global Research & Development)

  • Toyotaka Sato

    (Hokkaido University
    Hokkaido University)

  • Kazuki Yamamoto

    (Hokkaido University
    Hokkaido University)

  • Yuta Hikiji

    (Hokkaido University)

  • Akira Katsuyama

    (Hokkaido University
    Hokkaido University
    Hokkaido University)

  • Motoko Shinohara

    (Fujita Health University School of Medicine)

  • Yusuke Minato

    (Fujita Health University School of Medicine)

  • Satoshi Takahashi

    (Sapporo Medical University Hospital
    Sapporo Medical University School of Medicine)

  • Motohiro Horiuchi

    (Hokkaido University
    Hokkaido University)

  • Shin-ichi Yokota

    (Sapporo Medical University School of Medicine)

  • Seok-Yong Lee

    (Duke University School of Medicine)

  • Satoshi Ichikawa

    (Hokkaido University
    Hokkaido University
    Hokkaido University)

Abstract

The development of new antibacterial drugs with different mechanisms of action is urgently needed to address antimicrobial resistance. MraY is an essential membrane enzyme required for bacterial cell wall synthesis. Sphaerimicins are naturally occurring macrocyclic nucleoside inhibitors of MraY and are considered a promising target in antibacterial discovery. However, developing sphaerimicins as antibacterials has been challenging due to their complex macrocyclic structures. In this study, we construct their characteristic macrocyclic skeleton via two key reactions. Having then determined the structure of a sphaerimicin analogue bound to MraY, we use a structure-guided approach to design simplified sphaerimicin analogues. These analogues retain potency against MraY and exhibit potent antibacterial activity against Gram-positive bacteria, including clinically isolated drug resistant strains of S. aureus and E. faecium. Our study combines synthetic chemistry, structural biology, and microbiology to provide a platform for the development of MraY inhibitors as antibacterials against drug-resistant bacteria.

Suggested Citation

  • Takeshi Nakaya & Miyuki Yabe & Ellene H. Mashalidis & Toyotaka Sato & Kazuki Yamamoto & Yuta Hikiji & Akira Katsuyama & Motoko Shinohara & Yusuke Minato & Satoshi Takahashi & Motohiro Horiuchi & Shin-, 2022. "Synthesis of macrocyclic nucleoside antibacterials and their interactions with MraY," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35227-z
    DOI: 10.1038/s41467-022-35227-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-35227-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-35227-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ellene H. Mashalidis & Benjamin Kaeser & Yuma Terasawa & Akira Katsuyama & Do-Yeon Kwon & Kiyoun Lee & Jiyong Hong & Satoshi Ichikawa & Seok-Yong Lee, 2019. "Chemical logic of MraY inhibition by antibacterial nucleoside natural products," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Eric D. Brown & Gerard D. Wright, 2016. "Antibacterial drug discovery in the resistance era," Nature, Nature, vol. 529(7586), pages 336-343, January.
    3. Ben C. Chung & Ellene H. Mashalidis & Tetsuya Tanino & Mijung Kim & Akira Matsuda & Jiyong Hong & Satoshi Ichikawa & Seok-Yong Lee, 2016. "Structural insights into inhibition of lipid I production in bacterial cell wall synthesis," Nature, Nature, vol. 533(7604), pages 557-560, May.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Abraham O. Oluwole & Robin A. Corey & Chelsea M. Brown & Victor M. Hernández-Rocamora & Phillip J. Stansfeld & Waldemar Vollmer & Jani R. Bolla & Carol V. Robinson, 2022. "Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Elsa Hansen & Jason Karslake & Robert J Woods & Andrew F Read & Kevin B Wood, 2020. "Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations," PLOS Biology, Public Library of Science, vol. 18(5), pages 1-20, May.
    3. Hajkowicz, Stefan & Naughtin, Claire & Sanderson, Conrad & Schleiger, Emma & Karimi, Sarvnaz & Bratanova, Alexandra & Bednarz, Tomasz, 2022. "Artificial intelligence for science – adoption trends and future development pathways," MPRA Paper 115464, University Library of Munich, Germany.
    4. Alberto Signoroni & Alessandro Ferrari & Stefano Lombardi & Mattia Savardi & Stefania Fontana & Karissa Culbreath, 2023. "Hierarchical AI enables global interpretation of culture plates in the era of digital microbiology," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Chenyuan Wang & Yushan Xia & Runming Wang & Jingru Li & Chun-Lung Chan & Richard Yi-Tsun Kao & Patrick H. Toy & Pak-Leung Ho & Hongyan Li & Hongzhe Sun, 2023. "Metallo-sideromycin as a dual functional complex for combating antimicrobial resistance," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. Asmalia Md-Lasim & Farah Shafawati Mohd-Taib & Mardani Abdul-Halim & Ahmad Mohiddin Mohd-Ngesom & Sheila Nathan & Shukor Md-Nor, 2021. "Leptospirosis and Coinfection: Should We Be Concerned?," IJERPH, MDPI, vol. 18(17), pages 1-17, September.
    7. Wei Li Thong & Yingxin Zhang & Ying Zhuo & Katherine J. Robins & Joanna K. Fyans & Abigail J. Herbert & Brian J. C. Law & Jason Micklefield, 2021. "Gene editing enables rapid engineering of complex antibiotic assembly lines," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    8. Zhiwen Liu & Kangli Guo & Liemei Yan & Kai Zhang & Ying Wang & Xiaokang Ding & Nana Zhao & Fu-Jian Xu, 2023. "Janus nanoparticles targeting extracellular polymeric substance achieve flexible elimination of drug-resistant biofilms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    9. Kade D. Roberts & Yan Zhu & Mohammad A. K. Azad & Mei-Ling Han & Jiping Wang & Lynn Wang & Heidi H. Yu & Andrew S. Horne & Jo-Anne Pinson & David Rudd & Nicolas H. Voelcker & Nitin A. Patil & Jinxin Z, 2022. "A synthetic lipopeptide targeting top-priority multidrug-resistant Gram-negative pathogens," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    10. Qian Zhang & Bin Song & Yanan Xu & Yunmin Yang & Jian Ji & Wenjun Cao & Jianping Lu & Jiali Ding & Haiting Cao & Binbin Chu & Jiaxu Hong & Houyu Wang & Yao He, 2023. "In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Sijia Guo & Shu Wang & Suze Ma & Zixin Deng & Wei Ding & Qi Zhang, 2022. "Radical SAM-dependent ether crosslink in daropeptide biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    12. Hesam Aldin Varpaei & Mohammad Yavari & Mohammad Mahdi Miremami & Amir Mahdi Farahani & Faeze Esmaeili & Saba Abachi & Pariya Onsori & Pedram Nouroozi & Hossein Esmaeili & Ali Kazemi, 2020. "Epidemiological Study of Antibiotic Self-Medication in Tehran 1399, A Descriptive Study," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 31(1), pages 23870-23875, October.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35227-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.