IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40980-w.html
   My bibliography  Save this article

A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases

Author

Listed:
  • Shuyun Ju

    (University of California)

  • Kaylee P. Kuzelka

    (University of Illinois at Urbana−Champaign)

  • Rui Guo

    (University of California)

  • Benjamin Krohn-Hansen

    (University of California)

  • Jianping Wu

    (University of California)

  • Satish K. Nair

    (University of Illinois at Urbana−Champaign
    University of Illinois at Urbana−Champaign)

  • Yang Yang

    (University of California
    University of California)

Abstract

Catalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvMVAV as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvMVAV and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.

Suggested Citation

  • Shuyun Ju & Kaylee P. Kuzelka & Rui Guo & Benjamin Krohn-Hansen & Jianping Wu & Satish K. Nair & Yang Yang, 2023. "A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40980-w
    DOI: 10.1038/s41467-023-40980-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40980-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-40980-w?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. U. T. Bornscheuer & G. W. Huisman & R. J. Kazlauskas & S. Lutz & J. C. Moore & K. Robins, 2012. "Engineering the third wave of biocatalysis," Nature, Nature, vol. 485(7397), pages 185-194, 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. Qiuge Zhang & Samira M. Azarin & Casim A. Sarkar, 2022. "Model-guided engineering of DNA sequences with predictable site-specific recombination rates," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Aiko Kurimoto & Seyed A. Nasseri & Camden Hunt & Mike Rooney & David J. Dvorak & Natalie E. LeSage & Ryan P. Jansonius & Stephen G. Withers & Curtis P. Berlinguette, 2023. "Bioelectrocatalysis with a palladium membrane reactor," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    3. Ziyi Zhou & Liang Zhang & Yuanxi Yu & Banghao Wu & Mingchen Li & Liang Hong & Pan Tan, 2024. "Enhancing efficiency of protein language models with minimal wet-lab data through few-shot learning," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Le Quang Anh Tuan, 2018. "Rational protein design for enhancing thermal stability of industrial enzymes," HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE - ENGINEERING AND TECHNOLOGY, HO CHI MINH CITY OPEN UNIVERSITY JOURNAL OF SCIENCE, HO CHI MINH CITY OPEN UNIVERSITY, vol. 8(1), pages 3-17.
    5. Ke Li & Yucheng Zhao & Jian Yang & Jinlou Gu, 2022. "Nanoemulsion-directed growth of MOFs with versatile architectures for the heterogeneous regeneration of coenzymes," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    6. Cottier, Thomas & Foltea, Marina & Jost, Dannie, 2012. "Is there a case to be made for a global patent system? The example of plant biotechnology," Papers 428, World Trade Institute.
    7. Wei Huang & Haitao Yuan & Huangsheng Yang & Xiaomin Ma & Shuyao Huang & Hongjie Zhang & Siming Huang & Guosheng Chen & Gangfeng Ouyang, 2023. "Green synthesis of stable hybrid biocatalyst using a hydrogen-bonded, π-π-stacking supramolecular assembly for electrochemical immunosensor," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    8. Kerr Ding & Michael Chin & Yunlong Zhao & Wei Huang & Binh Khanh Mai & Huanan Wang & Peng Liu & Yang Yang & Yunan Luo, 2024. "Machine learning-guided co-optimization of fitness and diversity facilitates combinatorial library design in enzyme engineering," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    9. Peihui Li & Songjun Hou & Qingqing Wu & Yijian Chen & Boyu Wang & Haiyang Ren & Jinying Wang & Zhaoyi Zhai & Zhongbo Yu & Colin J. Lambert & Chuancheng Jia & Xuefeng Guo, 2023. "The role of halogens in Au–S bond cleavage for energy-differentiated catalysis at the single-bond limit," Nature Communications, Nature, vol. 14(1), pages 1-7, 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:14:y:2023:i:1:d:10.1038_s41467-023-40980-w. 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.