IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32088-4.html
   My bibliography  Save this article

AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis

Author

Listed:
  • Hong Jie Zhu

    (Nanjing University)

  • Bo Zhang

    (Nanjing University)

  • Wanqing Wei

    (Nanjing University)

  • Shuang He Liu

    (Nanjing University)

  • Lang Xiang

    (Nanjing University)

  • Jiapeng Zhu

    (Nanjing University of Chinese Medicine)

  • Rui Hua Jiao

    (Nanjing University)

  • Yasuhiro Igarashi

    (Toyama Prefectural University)

  • Ghader Bashiri

    (The University of Auckland)

  • Yong Liang

    (Nanjing University)

  • Ren Xiang Tan

    (Nanjing University)

  • Hui Ming Ge

    (Nanjing University)

Abstract

Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1). We show through in vivo gene deletion, in vitro biochemical assay and isotope labelling experiments that AvmM catalyzes tandem dehydration and Michael-type addition to generate the core scaffold of 1. Mechanistic studies by crystallography, DFT calculations and MD simulations of AvmM reveal that the reactions are achieved with assistance from the special tenuazonic acid like moiety of substrate. Our results thus uncover an uncharacterized macrocyclization strategy in natural product biosynthesis.

Suggested Citation

  • Hong Jie Zhu & Bo Zhang & Wanqing Wei & Shuang He Liu & Lang Xiang & Jiapeng Zhu & Rui Hua Jiao & Yasuhiro Igarashi & Ghader Bashiri & Yong Liang & Ren Xiang Tan & Hui Ming Ge, 2022. "AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32088-4
    DOI: 10.1038/s41467-022-32088-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32088-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32088-4?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. Kristina Haslinger & Madeleine Peschke & Clara Brieke & Egle Maximowitsch & Max J. Cryle, 2015. "X-domain of peptide synthetases recruits oxygenases crucial for glycopeptide biosynthesis," Nature, Nature, vol. 521(7550), pages 105-109, May.
    2. Fredarla S. Miller & Kathryn K. Crone & Matthew R. Jensen & Sudipta Shaw & William R. Harcombe & Mikael H. Elias & Michael F. Freeman, 2021. "Conformational rearrangements enable iterative backbone N-methylation in RiPP biosynthesis," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Tom Bretschneider & Joel B. Heim & Daniel Heine & Robert Winkler & Benjamin Busch & Björn Kusebauch & Thilo Stehle & Georg Zocher & Christian Hertweck, 2013. "Vinylogous chain branching catalysed by a dedicated polyketide synthase module," Nature, Nature, vol. 502(7469), pages 124-128, October.
    4. Jonathan Dorival & Fanny Risser & Christophe Jacob & Sabrina Collin & Gerald Dräger & Cédric Paris & Benjamin Chagot & Andreas Kirschning & Arnaud Gruez & Kira J. Weissman, 2018. "Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    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. Yuchun Zhao & Xiangyang Liu & Zhihong Xiao & Jie Zhou & Xingyu Song & Xiaozheng Wang & Lijun Hu & Ying Wang & Peng Sun & Wenning Wang & Xinyi He & Shuangjun Lin & Zixin Deng & Lifeng Pan & Ming Jiang, 2023. "O-methyltransferase-like enzyme catalyzed diazo installation in polyketide biosynthesis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Mathias H. Hansen & Martina Adamek & Dumitrita Iftime & Daniel Petras & Frauke Schuseil & Stephanie Grond & Evi Stegmann & Max J. Cryle & Nadine Ziemert, 2023. "Resurrecting ancestral antibiotics: unveiling the origins of modern lipid II targeting glycopeptides," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Nguyet A. Nguyen & F. N. U. Vidya & Neela H. Yennawar & Hongwei Wu & Andrew C. McShan & Vinayak Agarwal, 2024. "Disordered regions in proteusin peptides guide post-translational modification by a flavin-dependent RiPP brominase," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Guifa Zhai & Yan Zhu & Guo Sun & Fan Zhou & Yangning Sun & Zhou Hong & Chuan Dong & Peter F. Leadlay & Kui Hong & Zixin Deng & Fuling Zhou & Yuhui Sun, 2023. "Insights into azalomycin F assembly-line contribute to evolution-guided polyketide synthase engineering and identification of intermodular recognition," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Jialiang Wang & Xiaojie Wang & Xixi Li & LiangLiang Kong & Zeqian Du & Dandan Li & Lixia Gou & Hao Wu & Wei Cao & Xiaozheng Wang & Shuangjun Lin & Ting Shi & Zixin Deng & Zhijun Wang & Jingdan Liang, 2023. "C–N bond formation by a polyketide synthase," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    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_s41467-022-32088-4. 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.