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Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro

Author

Listed:
  • Joongoo Lee

    (Northwestern University
    Pohang University of Science and Technology (POSTECH))

  • Jaime N. Coronado

    (University of Texas at Austin)

  • Namjin Cho

    (Pohang University of Science and Technology (POSTECH))

  • Jongdoo Lim

    (University of Texas at Austin)

  • Brandon M. Hosford

    (University of Texas at Austin)

  • Sangwon Seo

    (Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST)
    Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS))

  • Do Soon Kim

    (Northwestern University)

  • Camila Kofman

    (Northwestern University)

  • Jeffrey S. Moore

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

  • Andrew D. Ellington

    (University of Texas at Austin)

  • Eric V. Anslyn

    (University of Texas at Austin)

  • Michael C. Jewett

    (Northwestern University
    Interdisplinary Biological Sciences Graduate Program
    Chemistry of Life Processes Institute
    Robert H. Lurie Comprehensive Cancer Center)

Abstract

The ribosome is a macromolecular machine that catalyzes the sequence-defined polymerization of L-α-amino acids into polypeptides. The catalysis of peptide bond formation between amino acid substrates is based on entropy trapping, wherein the adjacency of transfer RNA (tRNA)-coupled acyl bonds in the P-site and the α-amino groups in the A-site aligns the substrates for coupling. The plasticity of this catalytic mechanism has been observed in both remnants of the evolution of the genetic code and modern efforts to reprogram the genetic code (e.g., ribosomal incorporation of non-canonical amino acids, ribosomal ester formation). However, the limits of ribosome-mediated polymerization are underexplored. Here, rather than peptide bonds, we demonstrate ribosome-mediated polymerization of pyridazinone bonds via a cyclocondensation reaction between activated γ-keto and α-hydrazino ester monomers. In addition, we demonstrate the ribosome-catalyzed synthesis of peptide-hybrid oligomers composed of multiple sequence-defined alternating pyridazinone linkages. Our results highlight the plasticity of the ribosome’s ancient bond-formation mechanism, expand the range of non-canonical polymeric backbones that can be synthesized by the ribosome, and open the door to new applications in synthetic biology.

Suggested Citation

  • Joongoo Lee & Jaime N. Coronado & Namjin Cho & Jongdoo Lim & Brandon M. Hosford & Sangwon Seo & Do Soon Kim & Camila Kofman & Jeffrey S. Moore & Andrew D. Ellington & Eric V. Anslyn & Michael C. Jewet, 2022. "Ribosome-mediated biosynthesis of pyridazinone oligomers in vitro," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33701-2
    DOI: 10.1038/s41467-022-33701-2
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    References listed on IDEAS

    as
    1. Takayuki Katoh & Ingo Wohlgemuth & Masanobu Nagano & Marina V. Rodnina & Hiroaki Suga, 2016. "Essential structural elements in tRNAPro for EF-P-mediated alleviation of translation stalling," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    2. Jason W. Chin, 2017. "Expanding and reprogramming the genetic code," Nature, Nature, vol. 550(7674), pages 53-60, October.
    3. Michael J. Hammerling & Brian R. Fritz & Danielle J. Yoesep & Do Soon Kim & Erik D. Carlson & Michael C. Jewett, 2020. "In vitro ribosome synthesis and evolution through ribosome display," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    4. Joongoo Lee & Kevin J. Schwarz & Do Soon Kim & Jeffrey S. Moore & Michael C. Jewett, 2020. "Ribosome-mediated polymerization of long chain carbon and cyclic amino acids into peptides in vitro," Nature Communications, Nature, vol. 11(1), pages 1-8, December.
    5. Rey W. Martin & Benjamin J. Des Soye & Yong-Chan Kwon & Jennifer Kay & Roderick G. Davis & Paul M. Thomas & Natalia I. Majewska & Cindy X. Chen & Ryan D. Marcum & Mary Grace Weiss & Ashleigh E. Stodda, 2018. "Cell-free protein synthesis from genomically recoded bacteria enables multisite incorporation of noncanonical amino acids," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    6. Joongoo Lee & Kenneth E. Schwieter & Andrew M. Watkins & Do Soon Kim & Hao Yu & Kevin J. Schwarz & Jongdoo Lim & Jaime Coronado & Michelle Byrom & Eric V. Anslyn & Andrew D. Ellington & Jeffrey S. Moo, 2019. "Expanding the limits of the second genetic code with ribozymes," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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