ACS Publications. Most Trusted. Most Cited. Most Read
Molecular Basis for Autocatalytic Backbone N-Methylation in RiPP Natural Product Biosynthesis

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Chem. Biol. 2018, 13, 10, 2989-2999
    Articles

    Molecular Basis for Autocatalytic Backbone N-Methylation in RiPP Natural Product Biosynthesis
    Click to copy article linkArticle link copied!

    • Chayanid Ongpipattanakul
      Chayanid Ongpipattanakul
      Department of Biochemistry  and  Institute for Genomic Biology, University of Illinois at Urbana−Champaign, Champaign, Illinois 61801, United States
      More by Chayanid Ongpipattanakul
    • Satish K. Nair*
      Satish K. Nair
      Department of Biochemistry,  Institute for Genomic Biology  and  Center for Biophysics and Quantitative Biology, University of Illinois at Urbana−Champaign, Champaign, Illinois 61801, United States
      *E-mail: [email protected]
      More by Satish K. Nair
      Orcidhttp://orcid.org/0000-0003-1790-1334
    Other Access OptionsSupporting Information (1)

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2018, 13, 10, 2989–2999
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.8b00668
    Published September 11, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    N-methylation of nucleic acids, proteins, and peptides is a chemical modification with significant impact on biological regulation. Despite the simplicity of the structural change, N-methylation can influence diverse functions including epigenetics, protein complex formation, and microtubule stability. While there are limited examples of N-methylation of the α-amino group of bacterial and eukaryotic proteins, there are no examples of catalysts that carry out post-translation methylation of backbone amides in proteins or peptides. Recent studies have identified enzymes that catalyze backbone N-methylation on a peptide substrate, a reaction with little biochemical precedent, in a family of ribosomally synthesized natural products produced in basidiomycetes. Here, we describe the crystal structures of Dendrothele bispora dbOphMA, a methyltransferase that catalyzes multiple N-methylations on the peptide backbone. We further carry out biochemical studies of this catalyst to determine the molecular details that promote this unusual chemical transformation. The structural and biochemical framework described here could facilitate biotechnological applications of catalysts for the rapid production of backbone N-methylated peptides.

    Copyright © 2018 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acschembio.8b00668.

    • Experimental details regarding efforts to establish in trans and in vitro activity and the sequence similarity network analysis (PDF)

    Accession Codes

    The structure factors and coordinates have been deposited in the Protein Data Bank with the accession code 6MJG (peptide+SAH complex) and 6MJF (SAH complex).

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 30 publications.

    1. Haoqian Liang, Youran Luo, Wilfred A. van der Donk. Substrate Specificity of a Methyltransferase Involved in the Biosynthesis of the Lantibiotic Cacaoidin. Biochemistry 2024, 63 (19) , 2493-2505. https://doi.org/10.1021/acs.biochem.4c00150
    2. Aileen R. Lee, Riley S. Carter, Aman S. Imani, Shravan R. Dommaraju, Graham A. Hudson, Douglas A. Mitchell, Michael F. Freeman. Discovery of Borosin Catalytic Strategies and Function through Bioinformatic Profiling. ACS Chemical Biology 2024, 19 (5) , 1116-1124. https://doi.org/10.1021/acschembio.4c00066
    3. Bingjie Li, Yuqian Sun, Xinyi Zhu, Siyu Qian, Jiayang Pu, Yuwen Guo, Haobo Wu, Liang Zhang, Yu Xin. Aggregation Interface and Rigid Spots Sustain the Stable Framework of a Thermophilic N-Demethylase. Journal of Agricultural and Food Chemistry 2023, 71 (14) , 5614-5629. https://doi.org/10.1021/acs.jafc.3c00877
    4. Xiaoyan Chen, Rachel M. Johnson, Bo Li. A Permissive Amide N-Methyltransferase for Dithiolopyrrolones. ACS Catalysis 2023, 13 (3) , 1899-1905. https://doi.org/10.1021/acscatal.2c05439
    5. Yiwu Zheng, Chayanid Ongpipattanakul, Satish K. Nair. Bioconjugate Platform for Iterative Backbone N-Methylation of Peptides. ACS Catalysis 2022, 12 (22) , 14006-14014. https://doi.org/10.1021/acscatal.2c04681
    6. Hyunjin Cho, Hyunbin Lee, Kyungtae Hong, Hannah Chung, Inseok Song, Jun-Seok Lee, Seokhee Kim. Bioinformatic Expansion of Borosins Uncovers Trans-Acting Peptide Backbone N-Methyltransferases in Bacteria. Biochemistry 2022, 61 (3) , 183-194. https://doi.org/10.1021/acs.biochem.1c00764
    7. Alexander A. Vinogradov, Masanobu Nagano, Yuki Goto, Hiroaki Suga. Site-Specific Nonenzymatic Peptide S/O-Glutamylation Reveals the Extent of Substrate Promiscuity in Glutamate Elimination Domains. Journal of the American Chemical Society 2021, 143 (33) , 13358-13369. https://doi.org/10.1021/jacs.1c06470
    8. Haigang Song, Ju̅ratè Fahrig-Kamarauskaitè, Emmanuel Matabaro, Hannelore Kaspar, Sally L. Shirran, Christina Zach, Amy Pace, Bozhidar-Adrian Stefanov, James H. Naismith, Markus Künzler. Substrate Plasticity of a Fungal Peptide α-N-Methyltransferase. ACS Chemical Biology 2020, 15 (7) , 1901-1912. https://doi.org/10.1021/acschembio.0c00237
    9. Marissa R. Quijano, Christina Zach, Fredarla S. Miller, Aileen R. Lee, Aman S. Imani, Markus Künzler, Michael F. Freeman. Distinct Autocatalytic α-N-Methylating Precursors Expand the Borosin RiPP Family of Peptide Natural Products. Journal of the American Chemical Society 2019, 141 (24) , 9637-9644. https://doi.org/10.1021/jacs.9b03690
    10. Nguyet A. Nguyen, F. N. U. Vidya, Neela H. Yennawar, Hongwei Wu, Andrew C. McShan, Vinayak Agarwal. Disordered regions in proteusin peptides guide post-translational modification by a flavin-dependent RiPP brominase. Nature Communications 2024, 15 (1) https://doi.org/10.1038/s41467-024-45593-5
    11. Lisa S. Mydy, Jordan Hungerford, Desnor N. Chigumba, Jamie R. Konwerski, Sarah C. Jantzi, Di Wang, Janet L. Smith, Roland D. Kersten. An intramolecular macrocyclase in plant ribosomal peptide biosynthesis. Nature Chemical Biology 2024, 20 (4) , 530-540. https://doi.org/10.1038/s41589-024-01552-1
    12. Derek A. Wong, Zachary M. Shaver, Maria D. Cabezas, Martin Daniel-Ivad, Katherine F. Warfel, Deepali V. Prasanna, Sarah E. Sobol, Regina Fernandez, Robert Nicol, Matthew P. DeLisa, Emily P. Balskus, Ashty S. Karim, Michael C. Jewett. Development of cell-free platforms for discovering, characterizing, and engineering post-translational modifications. 2024https://doi.org/10.1101/2024.03.25.586624
    13. Emmanuel Matabaro, Luca Witte, Fabio Gherlone, Eva Vogt, Hannelore Kaspar, Markus Künzler. Promiscuity of Omphalotin A Biosynthetic Enzymes Allows de novo Production of Non‐Natural Multiply Backbone N‐Methylated Peptide Macrocycles in Yeast. ChemBioChem 2024, 25 (3) https://doi.org/10.1002/cbic.202300626
    14. Xuefei Li, Ningchao Wang, Yuhang Liu, Weipiao Li, Xinyu Bai, Ping Liu, Chun-Yang He. Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development. Bioorganic Chemistry 2023, 141 , 106892. https://doi.org/10.1016/j.bioorg.2023.106892
    15. Taro Ozaki, Atsushi Minami, Hideaki Oikawa. Recent advances in the biosynthesis of ribosomally synthesized and posttranslationally modified peptides of fungal origin. The Journal of Antibiotics 2023, 76 (1) , 3-13. https://doi.org/10.1038/s41429-022-00576-w
    16. Hyunji Lee, Wilfred A. van der Donk. Macrocyclization and Backbone Modification in RiPP Biosynthesis. Annual Review of Biochemistry 2022, 91 (1) , 269-294. https://doi.org/10.1146/annurev-biochem-032620-104956
    17. Dillon P. Cogan, Agneya Bhushan, Reyvin Reyes, Lingyang Zhu, Jörn Piel, Satish K. Nair. Structure and mechanism for iterative amide N -methylation in the biosynthesis of channel-forming peptide cytotoxins. Proceedings of the National Academy of Sciences 2022, 119 (13) https://doi.org/10.1073/pnas.2116578119
    18. Yu Xin, Chen Shen, Mengwei Tang, Zitao Guo, Yi Shi, Zhenghua Gu, Jun Shao, Liang Zhang. Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase. Journal of Biological Chemistry 2022, 298 (3) , 101656. https://doi.org/10.1016/j.jbc.2022.101656
    19. Simon C. Kessler, Yit-Heng Chooi. Out for a RiPP: challenges and advances in genome mining of ribosomal peptides from fungi. Natural Product Reports 2022, 39 (2) , 222-230. https://doi.org/10.1039/D1NP00048A
    20. Fredarla S. Miller, Kathryn K. Crone, Matthew R. Jensen, Sudipta Shaw, William R. Harcombe, Mikael H. Elias, Michael F. Freeman. Conformational rearrangements enable iterative backbone N-methylation in RiPP biosynthesis. Nature Communications 2021, 12 (1) https://doi.org/10.1038/s41467-021-25575-7
    21. Emmanuel Matabaro, Hannelore Kaspar, Paul Dahlin, Daniel L. V. Bader, Claudia E. Murar, Florian Staubli, Christopher M. Field, Jeffrey W. Bode, Markus Künzler. Identification, heterologous production and bioactivity of lentinulin A and dendrothelin A, two natural variants of backbone N-methylated peptide macrocycle omphalotin A. Scientific Reports 2021, 11 (1) https://doi.org/10.1038/s41598-021-83106-2
    22. Inseok Song, Younghyeon Kim, Jaeseung Yu, Su Yong Go, Hong Geun Lee, Woon Ju Song, Seokhee Kim. Molecular mechanism underlying substrate recognition of the peptide macrocyclase PsnB. Nature Chemical Biology 2021, 17 (11) , 1123-1131. https://doi.org/10.1038/s41589-021-00855-x
    23. Haigang Song, Antony J. Burton, Sally L. Shirran, Jūratė Fahrig‐Kamarauskaitė, Hannelore Kaspar, Tom W. Muir, Markus Künzler, James H. Naismith. Engineering of a Peptide α‐N‐Methyltransferase to Methylate Non‐Proteinogenic Amino Acids. Angewandte Chemie 2021, 133 (26) , 14440-14444. https://doi.org/10.1002/ange.202100818
    24. Haigang Song, Antony J. Burton, Sally L. Shirran, Jūratė Fahrig‐Kamarauskaitė, Hannelore Kaspar, Tom W. Muir, Markus Künzler, James H. Naismith. Engineering of a Peptide α‐N‐Methyltransferase to Methylate Non‐Proteinogenic Amino Acids. Angewandte Chemie International Edition 2021, 60 (26) , 14319-14323. https://doi.org/10.1002/anie.202100818
    25. Chunyu Wu, Wilfred A van der Donk. Engineering of new-to-nature ribosomally synthesized and post-translationally modified peptide natural products. Current Opinion in Biotechnology 2021, 69 , 221-231. https://doi.org/10.1016/j.copbio.2020.12.022
    26. Manuel Montalbán-López, Thomas A. Scott, Sangeetha Ramesh, Imran R. Rahman, Auke J. van Heel, Jakob H. Viel, Vahe Bandarian, Elke Dittmann, Olga Genilloud, Yuki Goto, María José Grande Burgos, Colin Hill, Seokhee Kim, Jesko Koehnke, John A. Latham, A. James Link, Beatriz Martínez, Satish K. Nair, Yvain Nicolet, Sylvie Rebuffat, Hans-Georg Sahl, Dipti Sareen, Eric W. Schmidt, Lutz Schmitt, Konstantin Severinov, Roderich D. Süssmuth, Andrew W. Truman, Huan Wang, Jing-Ke Weng, Gilles P. van Wezel, Qi Zhang, Jin Zhong, Jörn Piel, Douglas A. Mitchell, Oscar P. Kuipers, Wilfred A. van der Donk. New developments in RiPP discovery, enzymology and engineering. Natural Product Reports 2021, 38 (1) , 130-239. https://doi.org/10.1039/D0NP00027B
    27. Emmanuel Matabaro, Haigang Song, Clara Chepkirui, Hannelore Kaspar, Luca Witte, James H. Naismith, Michael F. Freeman, Markus Künzler. Enzyme-mediated backbone N-methylation in ribosomally encoded peptides. 2021, 429-458. https://doi.org/10.1016/bs.mie.2021.04.014
    28. Haigang Song, James H Naismith. Enzymatic methylation of the amide bond. Current Opinion in Structural Biology 2020, 65 , 79-88. https://doi.org/10.1016/j.sbi.2020.06.004
    29. Eva Vogt, Markus Künzler. Discovery of novel fungal RiPP biosynthetic pathways and their application for the development of peptide therapeutics. Applied Microbiology and Biotechnology 2019, 103 (14) , 5567-5581. https://doi.org/10.1007/s00253-019-09893-x
    30. Shangwen Luo, Shi-Hui Dong. Recent Advances in the Discovery and Biosynthetic Study of Eukaryotic RiPP Natural Products. Molecules 2019, 24 (8) , 1541. https://doi.org/10.3390/molecules24081541
    31. Yu Su, Meng Han, Xianbin Meng, Yue Feng, Shizhong Luo, Changyuan Yu, Guojun Zheng, Shaozhou Zhu. Discovery and characterization of a novel C-terminal peptide carboxyl methyltransferase in a lassomycin-like lasso peptide biosynthetic pathway. Applied Microbiology and Biotechnology 2019, 103 (6) , 2649-2664. https://doi.org/10.1007/s00253-019-09645-x
    Download PDF
    Go to ACS Chemical Biology
    Get e-Alerts
    Get e-Alerts

    ACS Chemical Biology

    Cite this: ACS Chem. Biol. 2018, 13, 10, 2989–2999
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschembio.8b00668
    Published September 11, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

    Article Views

    1708

    Altmetric

    -

    Citations

    30
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.