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Triepoxide formation by a flavin-dependent monooxygenase in monensin biosynthesis

Author

Listed:
  • Qian Wang

    (The University of Texas at El Paso)

  • Ning Liu

    (Northwest University)

  • Yaming Deng

    (Northwest University)

  • Yuze Guan

    (Northwest University)

  • Hongli Xiao

    (Northwest University)

  • Tara A. Nitka

    (The University of Texas at El Paso)

  • Hui Yang

    (Northwest University)

  • Anju Yadav

    (The University of Texas at El Paso)

  • Lela Vukovic

    (The University of Texas at El Paso)

  • Irimpan I. Mathews

    (SLAC National Accelerator Laboratory)

  • Xi Chen

    (Northwest University)

  • Chu-Young Kim

    (The University of Texas at El Paso
    University of Illinois Urbana-Champaign)

Abstract

Monensin A is a prototypical natural polyether polyketide antibiotic. It acts by binding a metal cation and facilitating its transport across the cell membrane. Biosynthesis of monensin A involves construction of a polyene polyketide backbone, subsequent epoxidation of the alkenes, and, lastly, formation of cyclic ethers via epoxide-opening cyclization. MonCI, a flavin-dependent monooxygenase, is thought to transform all three alkenes in the intermediate polyketide premonensin A into epoxides. Our crystallographic study has revealed that MonCI’s exquisite stereocontrol is due to the preorganization of the active site residues which allows only one specific face of the alkene to approach the reactive C(4a)-hydroperoxyflavin moiety. Furthermore, MonCI has an unusually large substrate-binding cavity that can accommodate premonensin A in an extended or folded conformation which allows any of the three alkenes to be placed next to C(4a)-hydroperoxyflavin. MonCI, with its ability to perform multiple epoxidations on the same substrate in a stereospecific manner, demonstrates the extraordinary versatility of the flavin-dependent monooxygenase family of enzymes.

Suggested Citation

  • Qian Wang & Ning Liu & Yaming Deng & Yuze Guan & Hongli Xiao & Tara A. Nitka & Hui Yang & Anju Yadav & Lela Vukovic & Irimpan I. Mathews & Xi Chen & Chu-Young Kim, 2023. "Triepoxide formation by a flavin-dependent monooxygenase in monensin biosynthesis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41889-0
    DOI: 10.1038/s41467-023-41889-0
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    References listed on IDEAS

    as
    1. Kinya Hotta & Xi Chen & Robert S. Paton & Atsushi Minami & Hao Li & Kunchithapadam Swaminathan & Irimpan I. Mathews & Kenji Watanabe & Hideaki Oikawa & Kendall N. Houk & Chu-Young Kim, 2012. "Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis," Nature, Nature, vol. 483(7389), pages 355-358, March.
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