Computational design of myoglobin-based carbene transferases for monoterpene derivatization.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      Myoglobin*/chemistry ; Methane*/chemistry ; Methane*/analogs & derivatives ; Monoterpenes*/chemistry ; Monoterpenes*/metabolism; Protein Engineering/methods ; Transferases/chemistry ; Transferases/metabolism ; Molecular Docking Simulation
    • Abstract:
      Carbene transfer reactions have emerged as pivotal methodologies for the synthesis of complex molecular architectures. Heme protein-catalyzed carbene transfer reactions have shown promising results on model compounds. However, their limited substrate scope has hindered their application in natural product functionalization. Building upon the foundation of previously published work on a carbene transferase-myoglobin variant, this study employs computer-aided protein engineering to design myoglobin variants, using either docking or the deep learning-based LigandMPNN method. These variants were utilized as catalysts in carbene transfer reactions with a selection of monoterpene substrates featuring C-C double bonds, leading to seven target products. This cost-effective methodology broadens the substrate scope for heme protein-catalyzed reactions, thereby opening novel pathways for research in heme protein functionalities and offering fresh perspectives in the synthesis of bioactive molecules.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cyclopropanation; Monoterpene; Myoglobin; Natural product; Protein design
    • Accession Number:
      0 (Myoglobin)
      OP0UW79H66 (Methane)
      2465-56-7 (carbene)
      0 (Monoterpenes)
      EC 2.- (Transferases)
    • Publication Date:
      Date Created: 20240525 Date Completed: 20240614 Latest Revision: 20241011
    • Publication Date:
      20241011
    • Accession Number:
      10.1016/j.bbrc.2024.150160
    • Accession Number:
      38795453