Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Characterization of the Aminocarboxycyclopropane-Forming Enzyme CmaC

View Author Information
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, and Department of Chemistry, University of Illinois at Urbana−Champaign, Urbana, Illinois 61801
Cite this: Biochemistry 2007, 46, 2, 359–368
Publication Date (Web):December 16, 2006
https://doi.org/10.1021/bi061930j
Copyright © 2007 American Chemical Society

    Article Views

    1003

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Other access options
    Supporting Info (2)»

    Abstract

    Abstract Image

    The biosynthesis of the coronamic acid fragment of the pseudomonal phytotoxin coronatine involves construction of the cyclopropane ring from a γ-chloro-l-allo-Ile intermediate while covalently tethered as a phosphopantetheinyl thioester to the carrier protein CmaD. The cyclopropane-forming catalyst is CmaC, catalyzing an intramolecular displacement of the γ-Cl group by the α carbon. CmaC can be isolated as a Zn2+ protein with about 10-fold higher activity over the apo form. CmaC will not cyclize free γ-chloro amino acids or their S-N-acetylcysteamine (NAC) thioester derivatives but will recognize some other carrier protein scaffolds. Turnover numbers of 5 min-1 are observed for Zn−CmaC, acting on γ-chloro-l-aminobutyryl-S-CmaD, generating 1-aminocyclopropane-1-carbonyl (ACC)-S-CmaD. Products were detected either while still tethered to the phosphopantetheinyl prosthetic arm by mass spectrometry or after thioesterase-mediated release and derivatization of the free amino acid. In D2O, CmaC catalyzed exchange of one deuterium into the aminobutyryl moiety of the γ-Cl-aminoacyl-S-CmaD, whereas the product ACC-S-CmaD lacked the deuterium, consistent with a competition for a γ-Cl-aminobutyryl α-carbanion between reprotonation and cyclization. CmaC-mediated cyclization yielded solely ACC, resulting from C−C bond formation and no azetidine carboxylate from an alternate N−C cyclization. CmaC could cyclize γ,γ-dichloroaminobutyryl to the Cl-ACC product but did not cyclize δ- or ε-chloroaminoacyl-S-CmaD substrates.

    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. You can change your affiliated institution below.

     This work was supported in part by the National Institutes of Health GM 20011 (to C.T.W.), F32GM7215 (to W.L.K.), and GM 067725 (to N.L.K.), the Jane Coffin Childs Memorial Fund (to D.A.V.), and the Damon Runyon Cancer Research Foundation Postdoctoral Fellowship (DRG-1893-05 to D.G.).

     These authors contributed equally to this work.

    §

     Harvard Medical School.

     Present address:  School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332.

     University of Illinois at Urbana−Champaign.

    #

     Present address:  Department of Chemistry, Harvey Mudd College, Claremont, California 91711.

    *

     To whom correspondence should be addressed. E-mail: [email protected]. Telephone:  (617) 432-1715. Fax:  (617) 432-0438.

    Supporting Information Available

    ARTICLE SECTIONS
    Jump To

    Additional Materials and Methods and Figures S1−S4. This material is available free of charge via the Internet at http://pubs.acs.org.

    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

    This article is cited by 43 publications.

    1. Takeshi Nanjo, Ayaka Matsumoto, Takuma Oshita, Yoshiji Takemoto. Synthesis of Chlorinated Oligopeptides via γ- and δ-Selective Hydrogen Atom Transfer Enabled by the N-Chloropeptide Strategy. Journal of the American Chemical Society 2023, 145 (34) , 19067-19075. https://doi.org/10.1021/jacs.3c06931
    2. Sili Wang, Yiyuan Cheng, Xiaofeng Wang, Qian Yang, Wen Liu. Tracing of Acyl Carrier Protein-channeled Mitomycin Intermediates in Streptomyces caespitosus Facilitates Characterization of the Biosynthetic Steps for AHBA–GlcN Formation and Processing. Journal of the American Chemical Society 2022, 144 (32) , 14945-14956. https://doi.org/10.1021/jacs.2c06969
    3. Zhengren Xu, Guohui Pan, Hao Zhou, Ben Shen. Discovery and Characterization of 1-Aminocyclopropane-1-carboxylic Acid Synthase of Bacterial Origin. Journal of the American Chemical Society 2018, 140 (49) , 16957-16961. https://doi.org/10.1021/jacs.8b11463
    4. Vinayak Agarwal, Zachary D. Miles, Jaclyn M. Winter, Alessandra S. Eustáquio, Abrahim A. El Gamal, and Bradley S. Moore . Enzymatic Halogenation and Dehalogenation Reactions: Pervasive and Mechanistically Diverse. Chemical Reviews 2017, 117 (8) , 5619-5674. https://doi.org/10.1021/acs.chemrev.6b00571
    5. Jeremy C. Henderson, Christopher D. Fage, Joe R. Cannon, Jennifer S. Brodbelt, Adrian T. Keatinge-Clay, and M. Stephen Trent . Antimicrobial Peptide Resistance of Vibrio cholerae Results from an LPS Modification Pathway Related to Nonribosomal Peptide Synthetases. ACS Chemical Biology 2014, 9 (10) , 2382-2392. https://doi.org/10.1021/cb500438x
    6. Wei Huang, Hui Xu, Yan Li, Feng Zhang, Xin-Ya Chen, Qing-Li He, Yasuhiro Igarashi, and Gong-Li Tang . Characterization of Yatakemycin Gene Cluster Revealing a Radical S-Adenosylmethionine Dependent Methyltransferase and Highlighting Spirocyclopropane Biosynthesis. Journal of the American Chemical Society 2012, 134 (21) , 8831-8840. https://doi.org/10.1021/ja211098r
    7. Christopher J. Thibodeaux, Wei-chen Chang, and Hung-wen Liu . Enzymatic Chemistry of Cyclopropane, Epoxide, and Aziridine Biosynthesis. Chemical Reviews 2012, 112 (3) , 1681-1709. https://doi.org/10.1021/cr200073d
    8. Ute Galm, Evelyn Wendt-Pienkowski, Liyan Wang, Sheng-Xiong Huang, Claudia Unsin, Meifeng Tao, Jane M. Coughlin, and Ben Shen . Comparative Analysis of the Biosynthetic Gene Clusters and Pathways for Three Structurally Related Antitumor Antibiotics: Bleomycin, Tallysomycin, and Zorbamycin. Journal of Natural Products 2011, 74 (3) , 526-536. https://doi.org/10.1021/np1008152
    9. Christopher S. Neumann and Christopher T. Walsh. Biosynthesis of (−)-(1S,2R)-Allocoronamic Acyl Thioester by an FeII-Dependent Halogenase and a Cyclopropane-Forming Flavoprotein. Journal of the American Chemical Society 2008, 130 (43) , 14022-14023. https://doi.org/10.1021/ja8064667
    10. Christopher T. Walsh. The Chemical Versatility of Natural-Product Assembly Lines. Accounts of Chemical Research 2008, 41 (1) , 4-10. https://doi.org/10.1021/ar7000414
    11. Richiro Ushimaru. Three-membered ring formation catalyzed by α-ketoglutarate-dependent nonheme iron enzymes. Journal of Natural Medicines 2024, 78 (1) , 21-32. https://doi.org/10.1007/s11418-023-01760-4
    12. Christopher T. Walsh. Tailoring enzyme strategies and functional groups in biosynthetic pathways. Natural Product Reports 2023, 40 (2) , 326-386. https://doi.org/10.1039/D2NP00048B
    13. Elijah Abraham, Rebecca A. Butcher. Warhead assembly in a lethal pathogen. Nature Chemistry 2022, 14 (8) , 848-850. https://doi.org/10.1038/s41557-022-01013-z
    14. Suze Ma, Dhanaraju Mandalapu, Shu Wang, Qi Zhang. Biosynthesis of cyclopropane in natural products. Natural Product Reports 2022, 39 (5) , 926-945. https://doi.org/10.1039/D1NP00065A
    15. Michael Winn, Michael Rowlinson, Fanghua Wang, Luis Bering, Daniel Francis, Colin Levy, Jason Micklefield. Discovery, characterization and engineering of ligases for amide synthesis. Nature 2021, 593 (7859) , 391-398. https://doi.org/10.1038/s41586-021-03447-w
    16. Sanjoy Adak, Bradley S. Moore. Cryptic halogenation reactions in natural product biosynthesis. Natural Product Reports 2021, 12 https://doi.org/10.1039/D1NP00010A
    17. Matt J. Jaremko, Tony D. Davis, Joshua C. Corpuz, Michael D. Burkart. Type II non-ribosomal peptide synthetase proteins: structure, mechanism, and protein–protein interactions. Natural Product Reports 2020, 37 (3) , 355-379. https://doi.org/10.1039/C9NP00047J
    18. Wen-Bing Jin, Sheng Wu, Xiao-Hong Jian, Hua Yuan, Gong-Li Tang. A radical S-adenosyl-L-methionine enzyme and a methyltransferase catalyze cyclopropane formation in natural product biosynthesis. Nature Communications 2018, 9 (1) https://doi.org/10.1038/s41467-018-05217-1
    19. Dawn R. D. Bignell, Zhenlong Cheng, Luke Bown. The coronafacoyl phytotoxins: structure, biosynthesis, regulation and biological activities. Antonie van Leeuwenhoek 2018, 111 (5) , 649-666. https://doi.org/10.1007/s10482-017-1009-1
    20. Nicholas S. MacArthur, Charles E. Jakobsche. 6-Hydroxynorleucine: Syntheses and Applications of a Versatile Building Block. Organic Preparations and Procedures International 2017, 49 (6) , 480-513. https://doi.org/10.1080/00304948.2017.1380492
    21. Katja Gemperlein, Michael Hoffmann, Liujie Huo, Patrick Pilak, Lutz Petzke, Rolf Müller, Silke C. Wenzel. Synthetic biology approaches to establish a heterologous production system for coronatines. Metabolic Engineering 2017, 44 , 213-222. https://doi.org/10.1016/j.ymben.2017.09.009
    22. Blaine G. McCarthy, Nicholas S. MacArthur, Charles E. Jakobsche. A simple synthesis of 6-hydroxynorleucine based on the rearrangement of an N-nitrosodichloroacetamide. Tetrahedron Letters 2016, 57 (4) , 502-504. https://doi.org/10.1016/j.tetlet.2015.12.070
    23. Bo Pang, Min Wang, Wen Liu. Cyclization of polyketides and non-ribosomal peptides on and off their assembly lines. Natural Product Reports 2016, 33 (2) , 162-173. https://doi.org/10.1039/C5NP00095E
    24. Horst Lechner, Desiree Pressnitz, Wolfgang Kroutil. Biocatalysts for the formation of three- to six-membered carbo- and heterocycles. Biotechnology Advances 2015, 33 (5) , 457-480. https://doi.org/10.1016/j.biotechadv.2015.01.012
    25. Maria I. Vizcaino, Jason M. Crawford. The colibactin warhead crosslinks DNA. Nature Chemistry 2015, 7 (5) , 411-417. https://doi.org/10.1038/nchem.2221
    26. Xiaoying Bian, Alberto Plaza, Youming Zhang, Rolf Müller. Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety. Chemical Science 2015, 6 (5) , 3154-3160. https://doi.org/10.1039/C5SC00101C
    27. Christopher T. Walsh, Robert V. O'Brien, Chaitan Khosla. Nonproteinogenic Amino Acid Building Blocks for Nonribosomal Peptide and Hybrid Polyketide Scaffolds. Angewandte Chemie International Edition 2013, 52 (28) , 7098-7124. https://doi.org/10.1002/anie.201208344
    28. Christopher T. Walsh, Robert V. O'Brien, Chaitan Khosla. Nichtproteinogene Aminosäurebausteine für Peptidgerüste aus nichtribosomalen Peptiden und hybriden Polyketiden. Angewandte Chemie 2013, 125 (28) , 7238-7265. https://doi.org/10.1002/ange.201208344
    29. William Nasser, Corinne Dorel, Julien Wawrzyniak, Frédérique Van Gijsegem, Marie‐Christine Groleau, Eric Déziel, Sylvie Reverchon. Vfm a new quorum sensing system controls the virulence of D ickeya dadantii . Environmental Microbiology 2013, 15 (3) , 865-880. https://doi.org/10.1111/1462-2920.12049
    30. Gert Callebaut, Sven Mangelinckx, Loránd Kiss, Reijo Sillanpää, Ferenc Fülöp, Norbert De Kimpe. Asymmetric synthesis of α,β-diamino acid derivatives with an aziridine-, azetidine- and γ-lactone-skeleton via Mannich-type additions across α-chloro-N-sulfinylimines. Organic & Biomolecular Chemistry 2012, 10 (11) , 2326. https://doi.org/10.1039/c2ob06637h
    31. Claudia Wagner, Gabriele M. König. Mechanisms of Halogenation of Marine Secondary Metabolites. 2012, 977-1024. https://doi.org/10.1007/978-90-481-3834-0_19
    32. Ivonne Höfer, Max Crüsemann, Markus Radzom, Bernadette Geers, Daniel Flachshaar, Xiaofeng Cai, Axel Zeeck, Jörn Piel. Insights into the Biosynthesis of Hormaomycin, An Exceptionally Complex Bacterial Signaling Metabolite. Chemistry & Biology 2011, 18 (3) , 381-391. https://doi.org/10.1016/j.chembiol.2010.12.018
    33. Tobias A. M. Gulder, Michael F. Freeman, Jörn Piel. The Catalytic Diversity of Multimodular Polyketide Synthases: Natural Product Biosynthesis Beyond Textbook Assembly Rules. 2011https://doi.org/10.1007/128_2010_113
    34. Roland D. Kersten, Michael J. Meehan, Pieter C. Dorrestein. Applications of Modern Mass Spectrometry Techniques in Natural Products Chemistry. 2010, 83-137. https://doi.org/10.1016/B978-0-08-102690-8.00711-9
    35. Roland D. Kersten, Michael J. Meehan, Pieter C. Dorrestein. Applications of Modern Mass Spectrometry Techniques in Natural Products Chemistry. 2010, 389-456. https://doi.org/10.1016/B978-008045382-8.00711-5
    36. Liangcai Gu, Bo Wang, Amol Kulkarni, Todd W. Geders, Rashel V. Grindberg, Lena Gerwick, Kristina Håkansson, Peter Wipf, Janet L. Smith, William H. Gerwick, David H. Sherman. Metamorphic enzyme assembly in polyketide diversification. Nature 2009, 459 (7247) , 731-735. https://doi.org/10.1038/nature07870
    37. Yvonne Braun, Angela Smirnova, Helge Weingart, Alexander Schenk, Matthias Ullrich. Coronatine Gene Expression In Vitro and In Planta, and Protein Accumulation During Temperature Downshift in Pseudomonas syringae. Sensors 2009, 9 (6) , 4272-4285. https://doi.org/10.3390/s90604272
    38. Harald Gross, Joyce E. Loper. Genomics of secondary metabolite production by Pseudomonas spp.. Natural Product Reports 2009, 26 (11) , 1408. https://doi.org/10.1039/b817075b
    39. Stefanie B Bumpus, Neil L Kelleher. Accessing natural product biosynthetic processes by mass spectrometry. Current Opinion in Chemical Biology 2008, 12 (5) , 475-482. https://doi.org/10.1016/j.cbpa.2008.07.022
    40. Dario Meluzzi, Wei Hao Zheng, Mary Hensler, Victor Nizet, Pieter C. Dorrestein. Top-down mass spectrometry on low-resolution instruments: Characterization of phosphopantetheinylated carrier domains in polyketide and non-ribosomal biosynthetic pathways. Bioorganic & Medicinal Chemistry Letters 2008, 18 (10) , 3107-3111. https://doi.org/10.1016/j.bmcl.2007.10.104
    41. Christopher S. Neumann, Danica Galonić Fujimori, Christopher T. Walsh. Halogenation Strategies In Natural Product Biosynthesis. Chemistry & Biology 2008, 15 (2) , 99-109. https://doi.org/10.1016/j.chembiol.2008.01.006
    42. Elizabeth S. Sattely, Michael A. Fischbach, Christopher T. Walsh. Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways. Natural Product Reports 2008, 25 (4) , 757. https://doi.org/10.1039/b801747f
    43. Danica Galonić Fujimori, Siniša Hrvatin, Christopher S. Neumann, Matthias Strieker, Mohamed A. Marahiel, Christopher T. Walsh. Cloning and characterization of the biosynthetic gene cluster for kutznerides. Proceedings of the National Academy of Sciences 2007, 104 (42) , 16498-16503. https://doi.org/10.1073/pnas.0708242104