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Engineering of ATP synthase for enhancement of proton-to-ATP ratio

Author

Listed:
  • Hiroshi Ueno

    (The University of Tokyo)

  • Kiyoto Yasuda

    (The University of Tokyo)

  • Norie Hamaguchi-Suzuki

    (Chiba University
    Chiba University)

  • Riku Marui

    (The University of Tokyo)

  • Naruhiko Adachi

    (High Energy Accelerator Research Organization (KEK)
    University of Tsukuba)

  • Toshiya Senda

    (High Energy Accelerator Research Organization (KEK))

  • Takeshi Murata

    (Chiba University)

  • Hiroyuki Noji

    (The University of Tokyo)

Abstract

FoF1-ATP synthase (FoF1) interconverts the energy of the proton motive force (pmf) and that of ATP through the mechanical rotation. The H+/ATP ratio, one of the most crucial parameters in bioenergetics, varies among species due to differences in the number of H+-binding c-subunits, resulting in H+/ATP ratios ranging from 2.7 to 5. In this study, we seek to significantly enhance the H+/ATP ratio by employing an alternative approach that differs from that of nature. We engineer FoF1 to form multiple peripheral stalks, each bound to a proton-conducting a-subunit. The engineered FoF1 exhibits an H+/ATP ratio of 5.8, surpassing the highest ratios found in naturally occurring FoF1s, enabling ATP synthesis under low pmf conditions where wild-type enzymes cannot synthesize ATP. Structural analysis reveals that the engineered FoF1 forms up to three peripheral stalks and a-subunits. This study not only provides valuable insights into the H+-transport mechanism of FoF1 but also opens up possibilities for engineering the foundation of cellular bioenergetics.

Suggested Citation

  • Hiroshi Ueno & Kiyoto Yasuda & Norie Hamaguchi-Suzuki & Riku Marui & Naruhiko Adachi & Toshiya Senda & Takeshi Murata & Hiroyuki Noji, 2025. "Engineering of ATP synthase for enhancement of proton-to-ATP ratio," Nature Communications, Nature, vol. 16(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61227-w
    DOI: 10.1038/s41467-025-61227-w
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    References listed on IDEAS

    as
    1. Yannick Rondelez & Guillaume Tresset & Takako Nakashima & Yasuyuki Kato-Yamada & Hiroyuki Fujita & Shoji Takeuchi & Hiroyuki Noji, 2005. "Highly coupled ATP synthesis by F1-ATPase single molecules," Nature, Nature, vol. 433(7027), pages 773-777, February.
    2. Hiroyuki Noji & Ryohei Yasuda & Masasuke Yoshida & Kazuhiko Kinosita, 1997. "Direct observation of the rotation of F1-ATPase," Nature, Nature, vol. 386(6622), pages 299-302, March.
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