IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50141-2.html
   My bibliography  Save this article

Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction

Author

Listed:
  • Lei Wang

    (Jiangnan University
    Jiangnan University
    Jiangnan University)

  • Yaoyun Wu

    (Jiangnan University
    Jiangnan University
    Jiangnan University)

  • Jun Hu

    (Jiangnan University)

  • Dejing Yin

    (Jiangnan University)

  • Wanqing Wei

    (Jiangnan University
    Jiangnan University)

  • Jian Wen

    (Jiangnan University)

  • Xiulai Chen

    (Jiangnan University
    Jiangnan University)

  • Cong Gao

    (Jiangnan University
    Jiangnan University)

  • Yiwen Zhou

    (Jiangnan University)

  • Jia Liu

    (Jiangnan University
    Jiangnan University)

  • Guipeng Hu

    (Jiangnan University)

  • Xiaomin Li

    (Jiangnan University
    Jiangnan University)

  • Jing Wu

    (Jiangnan University)

  • Zhi Zhou

    (Jiangnan University)

  • Liming Liu

    (Jiangnan University
    Jiangnan University)

  • Wei Song

    (Jiangnan University)

Abstract

Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Suggested Citation

  • Lei Wang & Yaoyun Wu & Jun Hu & Dejing Yin & Wanqing Wei & Jian Wen & Xiulai Chen & Cong Gao & Yiwen Zhou & Jia Liu & Guipeng Hu & Xiaomin Li & Jing Wu & Zhi Zhou & Liming Liu & Wei Song, 2024. "Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50141-2
    DOI: 10.1038/s41467-024-50141-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50141-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-50141-2?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. Xiaoqiang Huang & Binju Wang & Yajie Wang & Guangde Jiang & Jianqiang Feng & Huimin Zhao, 2020. "Photoenzymatic enantioselective intermolecular radical hydroalkylation," Nature, Nature, vol. 584(7819), pages 69-74, August.
    2. Praveen R. Juvvadi & David Fox & Benjamin G. Bobay & Michael J. Hoy & Sophie M. C. Gobeil & Ronald A. Venters & Zanetta Chang & Jackie J. Lin & Anna Floyd Averette & D. Christopher Cole & Blake C. Bar, 2019. "Harnessing calcineurin-FK506-FKBP12 crystal structures from invasive fungal pathogens to develop antifungal agents," Nature Communications, Nature, vol. 10(1), pages 1-18, 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. Huanhuan Li & Yawen Huang & Fuqiang Chen & Zhigang Zeng & Frank Hollmann & Xin Wu & Xiyang Zhang & Peigao Duan & Hao Su & Jianjun Shi & Xiang Sheng & Wuyuan Zhang, 2024. "Unspecific peroxygenase enabled formation of azoxy compounds," Nature Communications, Nature, vol. 15(1), pages 1-8, 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:15:y:2024:i:1:d:10.1038_s41467-024-50141-2. 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.