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image of Anticancer Compounds from Myxobacteria: Current Scenario and Future Perspectives

Abstract

Natural products and their derivatives have played a dominant role in the development of therapeutic agents. Traditionally, most of the natural products developed for the effective treatment of different diseases have been sourced from plants. Natural product discovery has seen a shift of focus towards microorganisms due to the chemical diversity of bioactive products they synthesize. Myxobacteria produce a large variety of novel chemical entities with diverse structures and varied bioactivities. In the last few decades, secondary metabolites from different genera of myxobacteria have been recognized as harbouring potent anticancer activity. Several analogs of these anticancer compounds have been prepared to address the limitations such as, poor solubility, high toxicity and low production yield, in order to obtain the compounds in higher quantities with better pharmacological properties and target selectivity. For example, a semi-synthetic derivative of epothilone obtained from a strain of myxobacterium has been approved for clinical use against taxane-resistant breast cancer. The anticancer compounds from myxobacteria target microtubules, the cytoskeleton, vacuolar ATPase, methionine aminopeptidase, exportin, the proteasome or translation elongation factor to exert anticancer activity. The focus of this review is on the promising anticancer compounds produced by myxobacteria, their targets and their mechanisms of action in cancer cells.

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2025-07-04
2025-11-02

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References

  1. Singh S.B. Confronting the challenges of discovery of novel antibacterial agents. Bioorg. Med. Chem. Lett. 2014 24 16 3683 3689 10.1016/j.bmcl.2014.06.053
    [Google Scholar]
  2. Newman D.J. Cragg G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod. 2016 79 3 629 661 10.1021/acs.jnatprod.5b01055
    [Google Scholar]
  3. Demain A.L. Vaishnav P. Natural products for cancer chemotherapy. Microb. Biotechnol. 2011 4 6 687 699 10.1111/j.1751‑7915.2010.00221.x
    [Google Scholar]
  4. Olano C. Méndez C. Salas J.A. Antitumor compounds from marine actinomycetes. Mar. Drugs 2009 7 2 210 248 10.3390/md7020210
    [Google Scholar]
  5. Atanasov A.G. Waltenberger B. Pferschy-Wenzig E.M. Linder T. Wawrosch C. Uhrin P. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015 33 8 1582 1614 10.1016/j.biotechadv.2015.08.001
    [Google Scholar]
  6. Karpiński T.M. Adamczak A. Anticancer activity of bacterial proteins and peptides. Pharmaceutics 2018 10 2 54 10.3390/pharmaceutics10020054
    [Google Scholar]
  7. Umezawa H. Low-molecular-weight enzyme inhibitors of microbial origin. Annu. Rev. Microbiol. 1982 36 1 75 99 10.1146/annurev.mi.36.100182.000451 6293372
    [Google Scholar]
  8. Bérdy J. Bioactive microbial metabolites. J. Antibiot. 2005 58 1 1 26 10.1038/ja.2005.1
    [Google Scholar]
  9. Herrmann J. Fayad A.A. Müller R. Natural products from myxobacteria: novel metabolites and bioactivities. Nat. Prod. Rep. 2017 34 2 135 160 10.1039/c6np00106h
    [Google Scholar]
  10. Bader C.D. Panter F. Müller R. In depth natural product discovery - Myxobacterial strains that provided multiple secondary metabolites. Biotechnol. Adv. 2020 39 107480 10.1016/j.biotechadv.2019.107480 31707075
    [Google Scholar]
  11. Nett M. König G.M. The chemistry of gliding bacteria. Nat. Prod. Rep. 2007 24 6 1245 1261 10.1039/b612668p
    [Google Scholar]
  12. Bollag D.M. McQueney P.A. Zhu J. Hensens O. Koupal L. Liesch J. Goetz M. Lazarides E. Woods C.M. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res. 1995 55 11 2325 2333 [PMID: 7757983
    [Google Scholar]
  13. Tan A.R. Toppmeyer D.L. Ixabepilone in metastatic breast cancer: Complement or alternative to taxanes? Clin. Cancer Res. 2008 14 21 6725 6729 10.1158/1078‑0432.CCR‑07‑4704 18980963
    [Google Scholar]
  14. Xu B. Sun T. Zhang Q. Zhang P. Yuan Z. Jiang Z. Efficacy of utidelone plus capecitabine versus capecitabine for heavily pretreated, anthracycline- and taxane-refractory metastatic breast cancer: Final analysis of overall survival in a phase III randomised controlled trial. Ann. Oncol. 2021 32 2 218 228 10.1016/j.annonc.2020.10.600
    [Google Scholar]
  15. Menche D. Hassfeld J. Steinmetz H. Huss M. Wieczorek H. Sasse F. The first hydroxylated archazolid from the myxobacterium Cystobacter violaceus: Isolation, structural elucidation and V-ATPase inhibition. J. Antibiot. 2007 60 5 328 331 10.1038/ja.2007.43 17551213
    [Google Scholar]
  16. Sasse F. Kunze B. Gronewold T.M.A. Reichenbach H. The chondramides: Cytostatic agents from myxobacteria acting on the actin cytoskeleton. J. Natl. Cancer Inst. 1998 90 20 1559 1563 10.1093/jnci/90.20.1559 9790549
    [Google Scholar]
  17. Sasse F. Sieinmetz H. Heil J. Höfle G. Reichenbach H. Tubulysins, new cytostatic peptides from myxobacteria acting on microtubuli. Production, isolation, physico-chemical and biological properties. J. Antibiot. 2000 53 9 879 885 10.7164/antibiotics.53.879 11099220
    [Google Scholar]
  18. Wenzel S.C. Hoffmann H. Zhang J. Debussche L. Haag-Richter S. Kurz M. Nardi F. Lukat P. Kochems I. Tietgen H. Schummer D. Nicolas J.P. Calvet L. Czepczor V. Vrignaud P. Mühlenweg A. Pelzer S. Müller R. Brönstrup M. Production of the bengamide class of marine natural products in myxobacteria: Biosynthesis and structure–activity relationships. Angew. Chem. Int. Ed. 2015 54 51 15560 15564 10.1002/anie.201508277 26514647
    [Google Scholar]
  19. Hoffmann H. Kogler H. Heyse W. Matter H. Caspers M. Schummer D. Klemke-Jahn C. Bauer A. Penarier G. Debussche L. Brönstrup M. Discovery, structure elucidation, and biological characterization of nannocystin A, a macrocyclic myxobacterial metabolite with potent antiproliferative properties. Angew. Chem. Int. Ed. 2015 54 35 10145 10148 10.1002/anie.201411377 26031409
    [Google Scholar]
  20. Sasse F. Steinmetz H. Schupp T. Petersen F. Memmert K. Hofmann H. Heusser C. Brinkmann V. Matt P.V. Höfle G. Reichenbach H. Argyrins, immunosuppressive cyclic peptides from myxobacteria. I. Production, isolation, physico-chemical and biological properties. J. Antibiot. 2002 55 6 543 551 10.7164/antibiotics.55.543 12195959
    [Google Scholar]
  21. Köster M. Lykke-Andersen S. Elnakady Y.A. Gerth K. Washausen P. Höfle G. Sasse F. Kjems J. Hauser H. Ratjadones inhibit nuclear export by blocking CRM1/exportin 1. Exp. Cell Res. 2003 286 2 321 331 10.1016/S0014‑4827(03)00100‑9 12749860
    [Google Scholar]
  22. Sasse F. Steinmetz H. Höfle G. Reichenbach H. Archazolids, new cytotoxic macrolactones from Archangium gephyra (Myxobacteria). Production, isolation, physico-chemical and biological properties. J. Antibiot. 2003 56 6 520 525 10.7164/antibiotics.56.520 12931860
    [Google Scholar]
  23. Huss M. Sasse F. Kunze B. Jansen R. Steinmetz H. Ingenhorst G. Zeeck A. Wieczorek H. Archazolid and apicularen: Novel specific V-ATPase inhibitors. BMC Biochem. 2005 6 1 13 10.1186/1471‑2091‑6‑13 16080788
    [Google Scholar]
  24. Nishi T. Forgac M. The vacuolar (H+)-ATPases — Nature’s most versatile proton pumps. Nat. Rev. Mol. Cell Biol. 2002 3 2 94 103 10.1038/nrm729 11836511
    [Google Scholar]
  25. Hinton A. Bond S. Forgac M. V-ATPase functions in normal and disease processes. Pflugers Arch. 2009 457 3 589 598 10.1007/s00424‑007‑0382‑4 18026982
    [Google Scholar]
  26. Luong B. Schwenk R. Bräutigam J. Müller R. Menche D. Bischoff I. Fürst R. The vacuolar-type ATPase inhibitor archazolid increases tumor cell adhesion to endothelial cells by accumulating extracellular collagen. PLoS One 2018 13 9 e0203053 10.1371/journal.pone.0203053 30204757
    [Google Scholar]
  27. Bartel K. Müller R. von Schwarzenberg K. Differential regulation of AMP-activated protein kinase in healthy and cancer cells explains why V-ATPase inhibition selectively kills cancer cells. J. Biol. Chem. 2019 294 46 17239 17248 10.1074/jbc.RA119.010243 31604821
    [Google Scholar]
  28. von Schwarzenberg K. Wiedmann R.M. Oak P. Schulz S. Zischka H. Wanner G. Efferth T. Trauner D. Vollmar A.M. Mode of cell death induction by pharmacological vacuolar H+-ATPase (V-ATPase) inhibition. J. Biol. Chem. 2013 288 2 1385 1396 10.1074/jbc.M112.412007 23168408
    [Google Scholar]
  29. Merk H. Messer P. Ardelt M.A. Lamb D.C. Zahler S. Müller R. Vollmar A.M. Pachmayr J. Inhibition of the V-ATPase by Archazolid A: A new strategy to inhibit EMT. Mol. Cancer Ther. 2017 16 11 2329 2339 10.1158/1535‑7163.MCT‑17‑0129 28775146
    [Google Scholar]
  30. Wiedmann R.M. von Schwarzenberg K. Palamidessi A. Schreiner L. Kubisch R. Liebl J. Schempp C. Trauner D. Vereb G. Zahler S. Wagner E. Müller R. Scita G. Vollmar A.M. The V-ATPase-inhibitor archazolid abrogates tumor metastasis via inhibition of endocytic activation of the Rho-GTPase Rac1. Cancer Res. 2012 72 22 5976 5987 10.1158/0008‑5472.CAN‑12‑1772 22986742
    [Google Scholar]
  31. Bartel K. Winzi M. Ulrich M. Koeberle A. Menche D. Werz O. Müller R. Guck J. Vollmar A.M. von Schwarzenberg K. V-ATPase inhibition increases cancer cell stiffness and blocks membrane related Ras signaling - A new option for HCC therapy. Oncotarget 2017 8 6 9476 9487 10.18632/oncotarget.14339 28036299
    [Google Scholar]
  32. Hamm R. Zeino M. Frewert S. Efferth T. Up-regulation of cholesterol associated genes as novel resistance mechanism in glioblastoma cells in response to archazolid B. Toxicol. Appl. Pharmacol. 2014 281 1 78 86 10.1016/j.taap.2014.08.033 25218289
    [Google Scholar]
  33. Schneider L.S. von Schwarzenberg K. Lehr T. Ulrich M. Kubisch-Dohmen R. Liebl J. Trauner D. Menche D. Vollmar A.M. Vacuolar-ATPase inhibition blocks iron metabolism to mediate therapeutic effects in breast cancer. Cancer Res. 2015 75 14 2863 2874 10.1158/0008‑5472.CAN‑14‑2097 26018087
    [Google Scholar]
  34. Schneider L.S. Ulrich M. Lehr T. Menche D. Müller R. von Schwarzenberg K. MDM2 antagonist nutlin‐3a sensitizes tumors to V‐ATPase inhibition. Mol. Oncol. 2016 10 7 1054 1062 10.1016/j.molonc.2016.04.005 27157929
    [Google Scholar]
  35. Zhang S. Schneider L.S. Vick B. Grunert M. Jeremias I. Menche D. Müller R. Vollmar A.M. Liebl J. Anti-leukemic effects of the V-ATPase inhibitor Archazolid A. Oncotarget 2015 6 41 43508 43528 10.18632/oncotarget.6180 26496038
    [Google Scholar]
  36. Scheeff S. Rivière S. Ruiz J. Abdelrahman A. Schulz-Fincke A.C. Köse M. Tiburcy F. Wieczorek H. Gütschow M. Müller C.E. Menche D. Synthesis of novel potent archazolids: Pharmacology of an emerging class of anticancer drugs. J. Med. Chem. 2020 63 4 1684 1698 10.1021/acs.jmedchem.9b01887 31990540
    [Google Scholar]
  37. Scheeff S. Menche D. Total Synthesis of Archazolid F. Org. Lett. 2019 21 1 271 274 10.1021/acs.orglett.8b03715 30548075
    [Google Scholar]
  38. Menche D. Hassfeld J. Sasse F. Huss M. Wieczorek H. Design, synthesis, and biological evaluation of novel analogues of archazolid: A highly potent simplified V-ATPase inhibitor. Bioorg. Med. Chem. Lett. 2007 17 6 1732 1735 10.1016/j.bmcl.2006.12.073 17239591
    [Google Scholar]
  39. Menche D. Hassfeld J. Li J. Mayer K. Rudolph S. Modular total synthesis of archazolid A and B. J. Org. Chem. 2009 74 19 7220 7229 10.1021/jo901565n 19739663
    [Google Scholar]
  40. Stauch B. Simon B. Basile T. Schneider G. Malek N.P. Kalesse M. Carlomagno T. Elucidation of the structure and intermolecular interactions of a reversible cyclic-peptide inhibitor of the proteasome by NMR spectroscopy and molecular modeling. Angew. Chem. Int. Ed. 2010 49 23 3934 3938 10.1002/anie.201000140 20408152
    [Google Scholar]
  41. Kisselev A.F. Goldberg A.L. Proteasome inhibitors: From research tools to drug candidates. Chem. Biol. 2001 8 8 739 758 10.1016/S1074‑5521(01)00056‑4 11514224
    [Google Scholar]
  42. King R.W. Deshaies R.J. Peters J.M. Kirschner M.W. How proteolysis drives the cell cycle. Science 1996 274 5293 1652 1659 10.1126/science.274.5293.1652 8939846
    [Google Scholar]
  43. Hershko A. Roles of ubiquitin-mediated proteolysis in cell cycle control. Curr. Opin. Cell Biol. 1997 9 6 788 799 10.1016/S0955‑0674(97)80079‑8 9425343
    [Google Scholar]
  44. Wang X. Luo H. Chen H. Duguid W. Wu J. The Journal of Immunology. J. Immunol. 1998 157 10 4297 4308
    [Google Scholar]
  45. Cohen G.M. Caspases: The executioners of apoptosis In: Biochem. J 1997 326 (Pt 1) 1 16 10.1042/bj3260001
    [Google Scholar]
  46. Spataro V. Norbury C. Harris A.L. The ubiquitin-proteasome pathway in cancer. British J. Cancer Nat. Publish Group 1998 77 448 455
    [Google Scholar]
  47. Wieland M. Holm M. Rundlet E.J. Morici M. Koller T.O. Maviza T.P. Pogorevc D. Osterman I.A. Müller R. Blanchard S.C. Wilson D.N. The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation. Proc. Natl. Acad. Sci. USA 2022 119 19 e2114214119 10.1073/pnas.2114214119 35500116
    [Google Scholar]
  48. Nickeleit I. Zender S. Sasse F. Geffers R. Brandes G. Sörensen I. Steinmetz H. Kubicka S. Carlomagno T. Menche D. Gütgemann I. Buer J. Gossler A. Manns M.P. Kalesse M. Frank R. Malek N.P. Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition. Cancer Cell 2008 14 1 23 35 10.1016/j.ccr.2008.05.016 18598941
    [Google Scholar]
  49. Chen C.H. Genapathy S. Fischer P.M. Chan W.C. A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues. Org. Biomol. Chem. 2014 12 48 9764 9768 10.1039/C4OB02107J 25355299
    [Google Scholar]
  50. Allardyce D.J. Bell C.M. Loizidou E.Z. Argyrin B, a non‐competitive inhibitor of the human immunoproteasome exhibiting preference for β1i. Chem. Biol. Drug Des. 2019 94 2 1556 1567 10.1111/cbdd.13539 31074944
    [Google Scholar]
  51. Walter B. Canjuga D. Yüz S.G. Ghosh M. Bozko P. Przystal J.M. Govindarajan P. Anderle N. Keller A-L. Tatagiba M. Schenke-Layland K. Rammensee H-G. Stevanovic S. Malek N.P. Schmees C. Tabatabai G. Argyrin F treatment‐induced vulnerabilities lead to a novel combination therapy in experimental glioma. Adv. Ther. 2021 4 9 2100078 10.1002/adtp.202100078
    [Google Scholar]
  52. Nyfeler B. Hoepfner D. Palestrant D. Kirby C.A. Whitehead L. Yu R. Identification of elongation factor G as the conserved cellular target of argyrin B. PLoS One 2012 7 9 e42657 10.1371/journal.pone.0042657
    [Google Scholar]
  53. Almeida L. Dhillon-LaBrooy A. Castro C.N. Adossa N. Carriche G.M. Guderian M. Ribosome-targeting antibiotics impair t cell effector function and ameliorate autoimmunity by blocking mitochondrial protein synthesis. Immunity 2021 54 1 68 83 10.1016/j.immuni.2020.11.001
    [Google Scholar]
  54. Ley S.V. Priour A. Heusser C. Total synthesis of the cyclic heptapeptide Argyrin B: A new potent inhibitor of T-cell independent antibody formation. Org. Lett. 2002 4 5 711 714 10.1021/ol017184m 11869108
    [Google Scholar]
  55. Vollbrecht L. Steinmetz H. Höfle G. Oberer L. Rihs G. Bovermann G. Matt P.V. Argyrins, immunosuppressive cyclic peptides from myxobacteria. II. Structure elucidation and stereochemistry. J. Antibiot. 2002 55 8 715 721 10.7164/antibiotics.55.715 12374385
    [Google Scholar]
  56. Bülow L. Nickeleit I. Girbig A.K. Brodmann T. Rentsch A. Eggert U. Sasse F. Steinmetz H. Frank R. Carlomagno T. Malek N.P. Kalesse M. Synthesis and biological characterization of argyrin F. ChemMedChem 2010 5 6 832 836 10.1002/cmdc.201000080 20358576
    [Google Scholar]
  57. Gorelik T.E. Tehrani K.H.M.E. Gruene T. Monecke T. Niessing D. Kaiser U. Blankenfeldt W. Müller R. Crystal structure of natural product argyrin-D determined by 3D electron diffraction. CrystEngComm 2022 24 33 5885 5889 10.1039/D2CE00707J
    [Google Scholar]
  58. Pogorevc D. Tang Y. Hoffmann M. Zipf G. Bernauer H.S. Popoff A. Steinmetz H. Wenzel S.C. Biosynthesis and heterologous production of argyrins. ACS Synth. Biol. 2019 8 5 1121 1133 10.1021/acssynbio.9b00023 30995838
    [Google Scholar]
  59. Pogorevc D. Müller R. Biotechnological production optimization of argyrins – A potent immunomodulatory natural product class. Microb. Biotechnol. 2022 15 1 353 369 10.1111/1751‑7915.13959 34724343
    [Google Scholar]
  60. Adamczeski M. Quiñoà E. Crews P. Novel sponge-derived amino acids. 11. The entire absolute stereochemistry of the bengamides. J. Org. Chem. 1990 55 1 240 242 10.1021/jo00288a039
    [Google Scholar]
  61. White K.N. Tenney K. Crews P. The bengamides: A mini-review of natural sources, analogues, biological properties, biosynthetic origins, and future prospects. J. Nat. Prod. 2017 80 3 740 755 10.1021/acs.jnatprod.6b00970
    [Google Scholar]
  62. Hoffmann H. Bengamide derivatives, method for the production thereof and use thereof for the treatment of cancer IL Patent 174524A0 2005
  63. Bradshaw R.A. Expert opinion on therapeutic patents methionine aminopeptidase 2 inhibition: Antiangiogenesis and tumour therapy. 2005 Available from [https://www.tandfonline.com/action/journalInformation?journalCode=ietp20
    [Google Scholar]
  64. Johnson T.A. Sohn J. Vaske Y.M. White K.N. Cohen T.L. Vervoort H.C. Tenney K. Valeriote F.A. Bjeldanes L.F. Crews P. Myxobacteria versus sponge-derived alkaloids: The bengamide family identified as potent immune modulating agents by scrutiny of LC–MS/ELSD libraries. Bioorg. Med. Chem. 2012 20 14 4348 4355 10.1016/j.bmc.2012.05.043 22705020
    [Google Scholar]
  65. Phillips P.E. Bair K.W. Bontempo J. Crews P. Czuchta M. Kinder F.R. Bengamide E arrests cells at the G1/S restriction point and within the G2/M phase of the cell cycle. Proc. Am. Assoc. Cancer Res. 2000 1 9
    [Google Scholar]
  66. Hu X. Dang Y. Tenney K. Crews P. Tsai C.W. Sixt K.M. Cole P.A. Liu J.O. Regulation of c-Src nonreceptor tyrosine kinase activity by bengamide A through inhibition of methionine aminopeptidases. Chem. Biol. 2007 14 7 764 774 10.1016/j.chembiol.2007.05.010 17656313
    [Google Scholar]
  67. Esa R. Steinberg E. Dror D. Schwob O. Khajavi M. Maoz M. The role of methionine aminopeptidase 2 in lymphangiogenesis. Int. J. Mol. Sci. 2020 21 14 5148 10.3390/ijms21145148
    [Google Scholar]
  68. Sin N. Meng L. Wang M.Q.W. Wen J.J. Bornmann W.G. Crews C.M. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proc. Natl. Acad. Sci. USA 1997 94 12 6099 6103 10.1073/pnas.94.12.6099 9177176
    [Google Scholar]
  69. Soleimani A. Rahmani F. Ferns G.A. Ryzhikov M. Avan A. Hassanian S.M. Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer. Gene Elsevier BV 2020 726 144132 10.1016/j.gene.2019.144132
    [Google Scholar]
  70. Jansen R. Chondramides A~D, New antifungal and cytostatic depsipeptides from chondromyces crocatus (myxobacteria) production, physicochemical and biological properties. J. Antibiot. 1995 48 11 1262 1266 10.7164/antibiotics.48.1262 8557566
    [Google Scholar]
  71. Olson M.F. Sahai E. The actin cytoskeleton in cancer cell motility. Clin. Exp. Metastasis 2009 26 4 273 287 10.1007/s10585‑008‑9174‑2 18498004
    [Google Scholar]
  72. Yamaguchi H. Condeelis J. Regulation of the actin cytoskeleton in cancer cell migration and invasion. Biochim. Biophys. Acta Mol. Cell Res. 2007 1773 5 642 652 10.1016/j.bbamcr.2006.07.001 16926057
    [Google Scholar]
  73. Foerster F. Braig S. Moser C. Kubisch R. Busse J. Wagner E. Schmoeckel E. Mayr D. Schmitt S. Huettel S. Zischka H. Mueller R. Vollmar A.M. Targeting the actin cytoskeleton: Selective antitumor action via trapping PKCɛ. Cell Death Dis. 2014 5 8 e1398 10.1038/cddis.2014.363 25165884
    [Google Scholar]
  74. Menhofer M.H. Bartel D. Liebl J. Kubisch R. Busse J. Wagner E. Müller R. Vollmar A.M. Zahler S. In vitro and in vivo characterization of the actin polymerizing compound chondramide as an angiogenic inhibitor. Cardiovasc. Res. 2014 104 2 303 314 10.1093/cvr/cvu210 25239826
    [Google Scholar]
  75. Menhofer M.H. Kubisch R. Schreiner L. Zorn M. Foerster F. Mueller R. Raedler J.O. Wagner E. Vollmar A.M. Zahler S. The actin targeting compound Chondramide inhibits breast cancer metastasis via reduction of cellular contractility. PLoS One 2014 9 11 e112542 10.1371/journal.pone.0112542 25391145
    [Google Scholar]
  76. Pergola C. Schubert K. Pace S. Ziereisen J. Nikels F. Scherer O. Modulation of actin dynamics as potential macrophage subtype-targeting anti-tumour strategy. Sci. Rep. 2017 7 41434 10.1038/srep41434
    [Google Scholar]
  77. Pfitzer L. Moser C. Gegenfurtner F. Arner A. Foerster F. Atzberger C. Zisis T. Kubisch-Dohmen R. Busse J. Smith R. Timinszky G. Kalinina O.V. Müller R. Wagner E. Vollmar A.M. Zahler S. Targeting actin inhibits repair of doxorubicin-induced DNA damage: A novel therapeutic approach for combination therapy. Cell Death Dis. 2019 10 4 302 10.1038/s41419‑019‑1546‑9 30944311
    [Google Scholar]
  78. Caridi C.P. Plessner M. Grosse R. Chiolo I. Nuclear actin filaments in DNA repair dynamics. Nat. Cell Biol. 2019 21 9 1068 1077 10.1038/s41556‑019‑0379‑1
    [Google Scholar]
  79. Waldmann H. Hu T.S. Renner S. Menninger S. Tannert R. Oda T. Arndt H.D. Total synthesis of chondramide C and its binding mode to F-actin. Angew. Chem. Int. Ed. 2008 47 34 6473 6477 10.1002/anie.200801010 18624308
    [Google Scholar]
  80. Zhdanko A. Schmauder A. Ma C.I. Sibley L.D. Sept D. Sasse F. Maier M.E. Synthesis of chondramide A analogues with modified β-tyrosine and their biological evaluation. Chemistry 2011 17 47 13349 13357 10.1002/chem.201101978 22012705
    [Google Scholar]
  81. Jansen R. Irschik H. Reichenbach H. Wray V. Höfle G. Antibiotics from gliding bacteria, LIX. disorazoles, highly cytotoxic metabolites from the sorangicin‐producing bacterium Sorangium Cellulosum, Strain So ce12. Liebigs Ann. Chem. 1994 1994 8 759 773 10.1002/jlac.199419940802
    [Google Scholar]
  82. Irschik H. Jansen R. Gerth K. Höfle G. Reichenbach H. Disorazol A, an efficient inhibitor of eukaryotic organisms isolated from myxobacteria. J. Antibiot. 1995 48 1 31 35 10.7164/antibiotics.48.31 7868386
    [Google Scholar]
  83. Nicolaou K.C. Buchman M. Bellavance G. Krieger J. Subramanian P. Pulukuri K.K. Syntheses of cyclopropyl analogues of disorazoles A1 and B1 and their thiazole counterparts. J. Org. Chem. 2018 83 20 12374 12389 10.1021/acs.joc.8b02137 30277774
    [Google Scholar]
  84. Nicolaou K.C. Rigol S. Total synthesis in search of potent antibody–drug conjugate payloads. From the fundamentals to the translational. Acc. Chem. Res. 2019 52 1 127 139 10.1021/acs.accounts.8b00537 30575399
    [Google Scholar]
  85. Lizzadro L. Spieß O. Schinzer D. Total Synthesis of (−)-Disorazole C1. Org. Lett. 2021 23 12 4543 4547 10.1021/acs.orglett.1c01123 34037403
    [Google Scholar]
  86. Lizzadro L. Spieß O. Collisi W. Stadler M. Schinzer D. Extending the structure‐activity relationship of disorazole C 1: Exchanging the oxazole ring by thiazole and influence of chiral centers within the disorazole core on cytotoxicity. ChemBioChem 2022 23 20 e202200458 10.1002/cbic.202200458 35998215
    [Google Scholar]
  87. Nicolaou K.C. Bellavance G. Buchman M. Pulukuri K.K. Total syntheses of disorazoles A1 and B1 and full structural elucidation of disorazole B1. J. Am. Chem. Soc. 2017 139 44 15636 15639 10.1021/jacs.7b09843 29064682
    [Google Scholar]
  88. Ralston K.J. Ramstadius H.C. Brewster R.C. Niblock H.S. Hulme A.N. Self‐assembly of disorazole C 1 through a one‐pot alkyne metathesis homodimerization strategy. Angew. Chem. Int. Ed. 2015 54 24 7086 7090 10.1002/anie.201501922 25926364
    [Google Scholar]
  89. Speed A.W.H. Mann T.J. O’Brien R.V. Schrock R.R. Hoveyda A.H. Catalytic Z-selective cross-metathesis in complex molecule synthesis: A convergent stereoselective route to disorazole C1. J. Am. Chem. Soc. 2014 136 46 16136 16139 10.1021/ja509973r 25379808
    [Google Scholar]
  90. Hopkins C.D. Schmitz J.C. Chu E. Wipf P. Total synthesis of (-)-CP2-disorazole C1. Org. Lett. 2011 13 15 4088 4091 10.1021/ol2015994 21739942
    [Google Scholar]
  91. Gao Y. Birkelbach J. Fu C. Herrmann J. Irschik H. Morgenstern B. Hirschfelder K. Li R. Zhang Y. Jansen R. Müller R. The disorazole Z family of highly potent anticancer natural products from sorangium cellulosum: Structure, bioactivity, biosynthesis, and heterologous expression. Microbiol. Spectr. 2023 11 4 e00730 e23 10.1128/spectrum.00730‑23 37318329
    [Google Scholar]
  92. Tu Q. Herrmann J. Hu S. Raju R. Bian X. Zhang Y. Genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via Red/ET recombineering. Sci. Rep. 2016 6 21066 10.1038/srep21066
    [Google Scholar]
  93. Carvalho R. Reid R. Viswanathan N. Gramajo H. Julien B. The biosynthetic genes for disorazoles, potent cytotoxic compounds that disrupt microtubule formation. Gene 2005 359 1–2 91 98 10.1016/j.gene.2005.06.003 16084035
    [Google Scholar]
  94. Elnakady Y.A. Sasse F. Lünsdorf H. Reichenbach H. Disorazol A1, a highly effective antimitotic agent acting on tubulin polymerization and inducing apoptosis in mammalian cells. Biochem. Pharmacol. 2004 67 5 927 935 10.1016/j.bcp.2003.10.029 15104246
    [Google Scholar]
  95. Wipf P. Graham T.H. Vogt A. Sikorski R.P. Ducruet A.P. Lazo J.S. Cellular analysis of disorazole C and structure-activity relationship of analogs of the natural product. Chem. Biol. Drug Des. 2006 67 1 66 73 10.1111/j.1747‑0285.2005.00313.x 16492150
    [Google Scholar]
  96. Tierno M.B. Kitchens C.A. Petrik B. Graham T.H. Wipf P. Xu F.L. Saunders W.S. Raccor B.S. Balachandran R. Day B.W. Stout J.R. Walczak C.E. Ducruet A.P. Reese C.E. Lazo J.S. Microtubule binding and disruption and induction of premature senescence by disorazole C(1). J. Pharmacol. Exp. Ther. 2009 328 3 715 722 10.1124/jpet.108.147330 19066338
    [Google Scholar]
  97. Wu S. Guo Z. Hopkins C.D. Wei N. Chu E. Wipf P. Schmitz J.C. Bis-cyclopropane analog of disorazole C1 is a microtubule-destabilizing agent active in abcb1-overexpressing human colon cancer cells. Oncotarget 2015 6 38 40866 40879 10.18632/oncotarget.5885 26506423
    [Google Scholar]
  98. Nicolaou K.C. Krieger J. Murhade G.M. Subramanian P. Dherange B.D. Vourloumis D. Munneke S. Lin B. Gu C. Sarvaiaya H. Sandoval J. Zhang Z. Aujay M. Purcell J.W. Gavrilyuk J. Streamlined symmetrical total synthesis of disorazole B 1 and design, synthesis, and biological investigation of disorazole analogues. J. Am. Chem. Soc. 2020 142 36 15476 15487 10.1021/jacs.0c07094 32852944
    [Google Scholar]
  99. Bold C.P. Lucena-Agell D. Oliva M.Á. Díaz J.F. Altmann K.H. Synthesis and biological evaluation of C(13)/C(13′)‐Bis(desmethyl)disorazole Z. Angew. Chem. Int. Ed. 2023 62 5 e202212190 10.1002/anie.202212190 36281761
    [Google Scholar]
  100. Gerth K. Bedorf N. Höfle G. Irschik H. Reichenbach H. Epothilons A and B: Antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties. J. Antibiot. 1996 49 6 560 563 10.7164/antibiotics.49.560 8698639
    [Google Scholar]
  101. Altmann K.H. Kinghorn A.D. Höfle G. Müller R. Prantz K. The epothilones: An outstanding family of anti-tumor agents: from soil to the clinic. Cham Springer 2009 1 5 10.1007/978‑3‑211‑78207‑1
    [Google Scholar]
  102. Höfle G. Bedorf N. Steinmetz H. Schomburg D. Gerth K. Reichenbach H. Epothilone A and B—Novel 16‐membered macrolides with cytotoxic activity: Isolation, crystal structure, and conformation in solution. Angew. Chem. Int. Ed. Engl. 1996 35 13-14 1567 1569 10.1002/anie.199615671
    [Google Scholar]
  103. Bode C.J. Gupta M.L. Reiff E.A. Suprenant K.A. Georg G.I. Himes R.H. Epothilone and paclitaxel: Unexpected differences in promoting the assembly and stabilization of yeast microtubules. Biochemistry 2002 41 12 3870 3874 10.1021/bi0121611 11900528
    [Google Scholar]
  104. Horwitz S.B. Taxol (paclitaxel): Mechanisms of action. Ann. Oncol. 1994 5 Suppl. 6 S3 S6 [PMID: 7865431
    [Google Scholar]
  105. Gradishar W.J. Taxanes for the treatment of metastatic breast cancer. Breast Cancer 2012 6 BCBCR.S8205. 10.4137/BCBCR.S8205 23133315
    [Google Scholar]
  106. Rowinsky E.K. Eisenhauer E.A. Chaudhry V. Arbuck S.G. Donehower R.C. Clinical toxicities encountered with paclitaxel (Taxol). Semin. Oncol. 1993 20 4 Suppl. 3 1 15
    [Google Scholar]
  107. Orr G.A. Verdier-Pinard P. McDaid H. Horwitz S.B. Mechanisms of taxol resistance related to microtubules. Oncogene 2003 22 47 7280 7295 10.1038/sj.onc.1206934 14576838
    [Google Scholar]
  108. Burkhart C.A. Kavallaris M. Band Horwitz S. The role of β-tubulin isotypes in resistance to antimitotic drugs. Biochim. Biophys. Acta 2001 1471 2 O1 O9 10.1016/s0304‑419x(00)00022‑6 11342188
    [Google Scholar]
  109. Pajeva I.K. Wiese M. Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J. Med. Chem. 2002 45 26 5671 5686 10.1021/jm020941h 12477351
    [Google Scholar]
  110. Meng D. Bertinato P. Balog A. Su D.S. Kamenecka T. Sorensen E.J. Danishefsky S.J. Total syntheses of epothilones A and B. J. Am. Chem. Soc. 1997 119 42 10073 10092 10.1021/ja971946k
    [Google Scholar]
  111. Nicolaou K.C. Sarabia F. Ninkovic S. Yang Z. Totalsynthese von Epothilon A durch Makrolactonisierung. Angew. Chem. 1997 109 5 539 540 10.1002/ange.19971090523
    [Google Scholar]
  112. Julien B. Shah S. Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus. Antimicrob. Agents Chemother. 2002 46 9 2772 2778 10.1128/AAC.46.9.2772‑2778.2002 12183227
    [Google Scholar]
  113. Schinzer D. Limberg A. Bauer A. Böhm O.M. Cordes M. Totalsynthese von (−)‐Epothilon A. Angew. Chem. 1997 109 5 543 544 10.1002/ange.19971090525
    [Google Scholar]
  114. Lee F.Y.F. Borzilleri R. Fairchild C.R. Kamath A. Smykla R. Kramer R. Vite G. Preclinical discovery of ixabepilone, a highly active antineoplastic agent. Cancer Chemother. Pharmacol. 2008 63 1 157 166 10.1007/s00280‑008‑0724‑8 18347795
    [Google Scholar]
  115. Ibrahim N.K. Ixabepilone: Overview of effectiveness, safety, and tolerability in metastatic breast cancer. Front. Oncol. 2021 11 617874 10.3389/fonc.2021.617874 34295806
    [Google Scholar]
  116. Nicolaou K.C. Shelke Y.G. Dherange B.D. Kempema A. Lin B. Gu C. Sandoval J. Hammond M. Aujay M. Gavrilyuk J. Design, synthesis, and biological investigation of epothilone B analogues featuring lactone, lactam, and carbocyclic macrocycles, epoxide, aziridine, and 1,1-Difluorocyclopropane and other fluorine residues. J. Org. Chem. 2020 85 5 2865 2917 10.1021/acs.joc.0c00123 32065746
    [Google Scholar]
  117. Xu Y. Qian L. Fang M. Liu Y. Xu Z.J. Ge X. Zhang Z. Liu Z.P. Lou H. Tumor selective self-assembled nanomicelles of carbohydrate-epothilone B conjugate for targeted chemotherapy. Eur. J. Med. Chem. 2023 259 115693 10.1016/j.ejmech.2023.115693 37531745
    [Google Scholar]
  118. Krastel P. Roggo S. Schirle M. Ross N.T. Perruccio F. Aspesi P. Aust T. Buntin K. Estoppey D. Liechty B. Mapa F. Memmert K. Miller H. Pan X. Riedl R. Thibaut C. Thomas J. Wagner T. Weber E. Xie X. Schmitt E.K. Hoepfner D. Nannocystin A. An elongation factor 1 inhibitor from myxobacteria with differential anti‐cancer properties. Angew. Chem. Int. Ed. 2015 54 35 10149 10154 10.1002/anie.201505069 26179970
    [Google Scholar]
  119. Zhang W. Wang J. Shan C. The eEF1A protein in cancer: Clinical significance, oncogenic mechanisms, and targeted therapeutic strategies. Pharmacol. Res. 2024 204 107195 10.1016/j.phrs.2024.107195 38677532
    [Google Scholar]
  120. Hotokezaka Y. Többen U. Hotokezaka H. van Leyen K. Beatrix B. Smith D.H. Nakamura T. Wiedmann M. Interaction of the eukaryotic elongation factor 1A with newly synthesized polypeptides. J. Biol. Chem. 2002 277 21 18545 18551 10.1074/jbc.M201022200 11893745
    [Google Scholar]
  121. Chang R. Wang E. Mouse translation elongation factor eEF1A‐2 interacts with Prdx‐I to protect cells against apoptotic death induced by oxidative stress. J. Cell. Biochem. 2007 100 2 267 278 10.1002/jcb.20969 16888816
    [Google Scholar]
  122. Sun Y. Du C. Wang B. Zhang Y. Liu X. Ren G. Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer. Biochem. Biophys. Res. Commun. 2014 450 1 1 6 10.1016/j.bbrc.2014.05.045 24853801
    [Google Scholar]
  123. Hou Y. Liu R. Xia M. Sun C. Zhong B. Yu J. Ai N. Lu J.J. Ge W. Liu B. Chen X. Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo. Pharmacol. Res. 2021 173 105870 10.1016/j.phrs.2021.105870 34500061
    [Google Scholar]
  124. Poock C. Kalesse M. Total synthesis of nannocystin Ax. Org. Lett. 2017 19 17 4536 4539 10.1021/acs.orglett.7b02112 28809579
    [Google Scholar]
  125. Miyakita D. Kawanishi K. Katsuyama A. Yamamoto K. Yakushiji F. Ichikawa S. Solid-phase synthesis of nannocystin Ax and its analogues. J. Org. Chem. 2023 88 15 11367 11371 10.1021/acs.joc.3c01189 37466434
    [Google Scholar]
  126. Huang J. Wang Z. Total syntheses of nannocystins A and A0, two elongation Factor 1 inhibitors. Org. Lett. 2016 18 18 4702 4705 10.1021/acs.orglett.6b02352 27598405
    [Google Scholar]
  127. Sun C. Liu R. Xia M. Hou Y. Wang X. Nannocystin Ax, a natural elongation factor 1α inhibitor from Nannocystis sp., suppresses epithelial-mesenchymal transition, adhesion and migration in lung cancer cells. Toxicol. Appl. Pharmacol. 2021 420 115535 10.1016/j.taap.2021.115535
    [Google Scholar]
  128. Zhang H. Xie F. Yuan X. Dai X. Tian Y. Sun M. Yu S. Cai J. Sun B. Zhang W. Shan C. Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1. Acta Pharmacol. Sin. 2024 45 5 1044 1059 10.1038/s41401‑024‑01231‑w 38326625
    [Google Scholar]
  129. Schummer D. Gerth K. Reichenbach H. Höfle G. Antibiotics from gliding bacteria, LXIII. Ratjadone: A new antifungal metabolite from Sorangium cellulosum. Liebigs Ann. 1995 1995 4 685 688 10.1002/jlac.199519950497
    [Google Scholar]
  130. Williams D.R. Ihle D.C. Plummer S.V. Total synthesis of (-)-ratjadone. Org. Lett. 2001 3 9 1383 1386 10.1021/ol015753k 11348240
    [Google Scholar]
  131. Bhatt U. Christmann M. Quitschalle M. Claus E. Kalesse M. The first total synthesis of +-ratjadone. J. Org. Chem. 2001 66 5 1885 1893 10.1021/jo005768g 11262141
    [Google Scholar]
  132. Cook A. Bono F. Jinek M. Conti E. Structural biology of nucleocytoplasmic transport. Annu. Rev. Biochem. 2007 76 1 647 671 10.1146/annurev.biochem.76.052705.161529 17506639
    [Google Scholar]
  133. Gravina G.L. Senapedis W. McCauley D. Baloglu E. Shacham S. Festuccia C. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J. Hematol. Oncol. 2014 7 1 85 10.1186/s13045‑014‑0085‑1 25476752
    [Google Scholar]
  134. Turner J.G. Dawson J. Sullivan D.M. Nuclear export of proteins and drug resistance in cancer. Biochem. Pharmacol. 2012 83 8 1021 1032 10.1016/j.bcp.2011.12.016 22209898
    [Google Scholar]
  135. Burzlaff A. Kalesse M. Kasper C. Scheper T. Multi parameter in vitro testing of ratjadone using flow cytometry. Appl. Microbiol. Biotechnol. 2003 62 2-3 174 179 10.1007/s00253‑003‑1300‑0 12679852
    [Google Scholar]
  136. Sun Q. Chen X. Zhou Q. Burstein E. Yang S. Jia D. Inhibiting cancer cell hallmark features through nuclear export inhibition. Signal Transduct. Target. Ther. 2016 1 16010 10.1038/sigtrans.2016.10
    [Google Scholar]
  137. Meissner T. Krause E. Vinkemeier U. Ratjadone and leptomycin B block CRM1‐dependent nuclear export by identical mechanisms. FEBS Lett. 2004 576 1-2 27 30 10.1016/j.febslet.2004.08.056 15474004
    [Google Scholar]
  138. Klahn P. Fetz V. Ritter A. Collisi W. Hinkelmann B. Arnold T. Tegge W. Rox K. Hüttel S. Mohr K.I. Wink J. Stadler M. Wissing J. Jänsch L. Brönstrup M. The nuclear export inhibitor aminoratjadone is a potent effector in extracellular-targeted drug conjugates. Chem. Sci. 2019 10 20 5197 5210 10.1039/C8SC05542D 31191875
    [Google Scholar]
  139. Sasse F. Steinmetz H. Höfle G. Reichenbach H. Rhizopodin, a new compound from Myxococcus stipitatus (myxobacteria) causes formation of rhizopodia-like structures in animal cell cultures. Production, isolation, physico-chemical and biological properties. J. Antibiot. 1993 46 5 741 748 10.7164/antibiotics.46.741 8514628
    [Google Scholar]
  140. Gronewold T.M.A. Sasse F. Lünsdorf H. Reichenbach H. Effects of rhizopodin and latrunculin B on the morphology and on the actin cytoskeleton of mammalian cells. Cell Tissue Res. 1999 295 1 121 129 10.1007/s004410051218 9931358
    [Google Scholar]
  141. Jansen R. Steinmetz H. Sasse F. Schubert W.D. Hagelüken G. Albrecht S.C. Müller R. Isolation and structure revision of the actin-binding macrolide rhizopodin from Myxococcus stipitatus (Myxobacteria). Tetrahedron Lett. 2008 49 40 5796 5799 10.1016/j.tetlet.2008.07.132
    [Google Scholar]
  142. Hagelueken G. Albrecht S.C. Steinmetz H. Jansen R. Heinz D.W. Kalesse M. Schubert W.D. The absolute configuration of rhizopodin and its inhibition of actin polymerization by dimerization. Angew. Chem. Int. Ed. 2009 48 3 595 598 10.1002/anie.200802915 19035596
    [Google Scholar]
  143. Herkommer D. Dreisigacker S. Sergeev G. Sasse F. Gohlke H. Menche D. Design, synthesis, and biological evaluation of simplified side chain hybrids of the potent actin binding polyketides rhizopodin and bistramide. ChemMedChem 2015 10 3 470 489 10.1002/cmdc.201402508 25641798
    [Google Scholar]
  144. Bender T. Loits D. White J.M. Rizzacasa M.A. Synthesis of the C1-C18 fragment of rhizopodin: Late-state introduction of the oxazole. Org. Lett. 2014 16 5 1450 1453 10.1021/ol500261n 24524264
    [Google Scholar]
  145. Pulukuri K.K. Chakraborty T.K. Formal synthesis of actin binding macrolide rhizopodin. Org. Lett. 2014 16 8 2284 2287 10.1021/ol5008179 24742162
    [Google Scholar]
  146. Chakraborty T.K. Sreekanth M. Pulukuri K.K. Synthetic studies toward potent cytostatic macrolide rhizopodin: Stereoselective synthesis of the C16–C28 fragment. Tetrahedron Lett. 2011 52 1 59 61 10.1016/j.tetlet.2010.10.142
    [Google Scholar]
  147. Dieckmann M. Rudolph S. Dreisigacker S. Menche D. Concise synthesis of the macrocyclic core of rhizopodin by a Heck macrocyclization strategy. J. Org. Chem. 2012 77 23 10782 10788 10.1021/jo302134y 23157362
    [Google Scholar]
  148. Dieckmann M. Kretschmer M. Li P. Rudolph S. Herkommer D. Menche D. Total synthesis of rhizopodin. Angew. Chem. Int. Ed. 2012 51 23 5667 5670 10.1002/anie.201201946 22532514
    [Google Scholar]
  149. Chen Z. Song L. Xu Z. Ye T. Synthesis of the C9-C23 (C9′-C23′) fragment of the dimeric natural product rhizopodin. Org. Lett. 2010 12 9 2036 2039 10.1021/ol100515m 20380407
    [Google Scholar]
  150. Kretschmer M. Dieckmann M. Li P. Rudolph S. Herkommer D. Troendlin J. Menche D. Modular total synthesis of rhizopodin: A highly potent G-actin dimerizing macrolide. Chemistry 2013 19 47 15993 16018 10.1002/chem.201302197 24123414
    [Google Scholar]
  151. Nicolaou K.C. Jiang X. Lindsay-Scott P.J. Corbu A. Yamashiro S. Bacconi A. Total synthesis and biological evaluation of monorhizopodin and 16-epi-monorhizopodin. Angew. Chem. Int. Ed. Engl. 2011 50 5 1139 1144 10.1002/anie.201006780
    [Google Scholar]
  152. Oku N. Matsumoto A. Matsunaga T. Asano Y. Kasai H. Matoba S. Igarashi Y. Two new ring-contracted congeners of rhizopodin illustrate significance of the ring moiety of macrolide toxins on the actin disassembly-mediated cytotoxicity. Chem. Pharm. Bull. 2014 62 3 294 300 10.1248/cpb.c13‑00856 24583785
    [Google Scholar]
  153. Pistorius D. Müller R. Discovery of the rhizopodin biosynthetic gene cluster in Stigmatella aurantiaca Sg a15 by genome mining. ChemBioChem 2012 13 3 416 426 10.1002/cbic.201100575 22278953
    [Google Scholar]
  154. Steinmetz H. Glaser N. Herdtweck E. Sasse F. Reichenbach H. Höfle G. Isolation, crystal and solution structure determination, and biosynthesis of tubulysins--powerful inhibitors of tubulin polymerization from myxobacteria. Angew. Chem. Int. Ed. 2004 43 37 4888 4892 10.1002/anie.200460147 15372566
    [Google Scholar]
  155. Chai Y. Pistorius D. Ullrich A. Weissman K.J. Kazmaier U. Müller R. Discovery of 23 natural tubulysins from Angiococcus disciformis An d48 and Cystobacter SBCb004. Chem. Biol. 2010 17 3 296 309 10.1016/j.chembiol.2010.01.016 20338521
    [Google Scholar]
  156. Cortes J. Baselga J. Targeting the microtubules in breast cancer beyond taxanes: The epothilones. Oncologist 2007 12 3 271 280 10.1634/theoncologist.12‑3‑271 17405891
    [Google Scholar]
  157. Khalil M.W. Sasse F. Lünsdorf H. Elnakady Y.A. Reichenbach H. Mechanism of action of tubulysin, an antimitotic peptide from myxobacteria. ChemBioChem 2006 7 4 678 683 10.1002/cbic.200500421 16491500
    [Google Scholar]
  158. a Kaur G. Hollingshead M. Holbeck S. Schauer-Vukašinović V. Camalier R.F. Dömling A. Biological evaluation of tubulysin A: A potential anticancer and antiangiogenic natural product. Biochem. J. 2006 396 2 235 242
    [Google Scholar]
  159. b Sandmann A. Sasse F. Müller R. Identification and analysis of the core biosynthetic machinery of tubulysin, a potent cytotoxin with potential anticancer activity. Chem. Biol. 2004 11 8 1071 1079 10.1016/j.chembiol.2004.05.014 15324808
    [Google Scholar]
  160. Chai Y. Shan S. Weissman K.J. Hu S. Zhang Y. Müller R. Heterologous expression and genetic engineering of the tubulysin biosynthetic gene cluster using Red/ET recombineering and inactivation mutagenesis. Chem. Biol. 2012 19 3 361 371 10.1016/j.chembiol.2012.01.007 22444591
    [Google Scholar]
  161. Peltier H.M. McMahon J.P. Patterson A.W. Ellman J.A. The total synthesis of tubulysin D. J. Am. Chem. Soc. 2006 128 50 16018 16019 10.1021/ja067177z 17165738
    [Google Scholar]
  162. Sasse F. Menche D. Success in tubulysin D synthesis. Nat. Chem. Biol. 2007 3 2 87 89 10.1038/nchembio0207‑87 17235344
    [Google Scholar]
  163. Wang Y. Cheetham A.G. Angacian G. Su H. Xie L. Cui H. Peptide-drug conjugates as effective prodrug strategies for targeted delivery. Adv. Drug Deliv. Rev. 2017 110–111 112 126 10.1016/j.addr.2016.06.015 27370248
    [Google Scholar]
  164. Cohen R. Vugts D.J. Visser G.W.M. Stigter-van Walsum M. Bolijn M. Spiga M. Lazzari P. Shankar S. Sani M. Zanda M. van Dongen G.A.M.S. Development of novel ADCs: Conjugation of tubulysin analogues to trastuzumab monitored by dual radiolabeling. Cancer Res. 2014 74 20 5700 5710 10.1158/0008‑5472.CAN‑14‑1141 25145670
    [Google Scholar]
  165. Roy J. Kaake M. Srinivasarao M. Low P.S. Targeted tubulysin B hydrazide conjugate for the treatment of luteinizing hormone-releasing hormone receptor-positive cancers. Bioconjug. Chem. 2018 29 7 2208 2214 10.1021/acs.bioconjchem.8b00164 29851465
    [Google Scholar]
  166. Drača D. Mijatović S. Krajnović T. Kaluđerović G.N. Wessjohann L.A. Maksimović-Ivanić D. Synthetic tubulysin derivative, tubugi-1, against invasive melanoma cells: The cell death triangle. Anticancer Res. 2019 39 10 5403 5415 10.21873/anticanres.13734 31570435
    [Google Scholar]
  167. Alqarni A. Elnakady Y.A. Alsadhan L. Abbas M. Richter W. Aldahmash B.A. Almansour M.I. Almutairi L.M. Rady A. Prospective mechanism of action of the tubulysin synthetic derivative (TAM 1344) in HCT116 colon cancer cell line. J. King Saud Univ. Sci. 2023 35 7 102824 10.1016/j.jksus.2023.102824
    [Google Scholar]
  168. Lamidi O.F. Sani M. Lazzari P. Zanda M. Fleming I.N. The tubulysin analogue KEMTUB10 induces apoptosis in breast cancer cells via p53, Bim and Bcl-2. J. Cancer Res. Clin. Oncol. 2015 141 9 1575 1583 10.1007/s00432‑015‑1921‑6 25633717
    [Google Scholar]
  169. Ullrich A. Chai Y. Pistorius D. Elnakady Y.A. Herrmann J.E. Weissman K.J. Kazmaier U. Müller R. Pretubulysin, a potent and chemically accessible tubulysin precursor from Angiococcus disciformis. Angew. Chem. Int. Ed. 2009 48 24 4422 4425 10.1002/anie.200900406 19431172
    [Google Scholar]
  170. Braig S. Wiedmann R.M. Liebl J. Singer M. Kubisch R. Schreiner L. Abhari B.A. Wagner E. Kazmaier U. Fulda S. Vollmar A.M. Pretubulysin: A new option for the treatment of metastatic cancer. Cell Death Dis. 2014 5 1 e1001 10.1038/cddis.2013.510 24434509
    [Google Scholar]
  171. Schwenk R. Stehning T. Bischoff I. Ullrich A. Kazmaier U. Fürst R. The pretubulysin-induced exposure of collagen is caused by endothelial cell retraction that results in an increased adhesion and decreased transmigration of tumor cells. Oncotarget 2017 8 44 77622 77633 10.18632/oncotarget.20746 29100413
    [Google Scholar]
  172. Rath S. Liebl J. Fürst R. Ullrich A. Burkhart J.L. Kazmaier U. Herrmann J. Müller R. Günther M. Schreiner L. Wagner E. Vollmar A.M. Zahler S. Anti‐angiogenic effects of the tubulysin precursor pretubulysin and of simplified pretubulysin derivatives. Br. J. Pharmacol. 2012 167 5 1048 1061 10.1111/j.1476‑5381.2012.02037.x 22595030
    [Google Scholar]
  173. Kubisch R. von Gamm M. Braig S. Ullrich A. Burkhart J.L. Colling L. Hermann J. Scherer O. Müller R. Werz O. Kazmaier U. Vollmar A.M. Simplified pretubulysin derivatives and their biological effects on cancer cells. J. Nat. Prod. 2014 77 3 536 542 10.1021/np4008014 24437936
    [Google Scholar]
  174. Xu X. Fan M. Qi J. Yao L. Design, synthesis, and antitumor activity evaluation of pretubulysin analogs. Chem. Biol. Drug Des. 2021 98 3 341 351 10.1111/cbdd.13852 33930251
    [Google Scholar]
  175. Weissman K.J. Müller R. Myxobacterial secondary metabolites: Bioactivities and modes-of-action. Nat. Prod. Rep. 2010 27 9 1276 1295 10.1039/c001260m 20520915
    [Google Scholar]
  176. Han K. Li Z. Peng R. Zhu L. Zhou T. Wang L. Li S. Zhang X. Hu W. Wu Z. Qin N. Li Y. Extraordinary expansion of a Sorangium cellulosum genome from an alkaline milieu. Sci. Rep. 2013 3 1 2101 10.1038/srep02101 23812535
    [Google Scholar]
  177. Chen R. Wong H.L. Burns B.P. New approaches to detect biosynthetic gene clusters in the environment. Medicines (Basel) 2019 6 1 32 10.3390/medicines6010032 30823559
    [Google Scholar]
  178. Gerth K. Pradella S. Perlova O. Beyer S. Müller R. Myxobacteria: Proficient producers of novel natural products with various biological activities—past and future biotechnological aspects with the focus on the genus Sorangium. J. Biotechnol. 2003 106 2-3 233 253 10.1016/j.jbiotec.2003.07.015 14651865
    [Google Scholar]
  179. Schneiker S. Perlova O. Kaiser O. Gerth K. Alici A. Altmeyer M.O. Bartels D. Bekel T. Beyer S. Bode E. Bode H.B. Bolten C.J. Choudhuri J.V. Doss S. Elnakady Y.A. Frank B. Gaigalat L. Goesmann A. Groeger C. Gross F. Jelsbak L. Jelsbak L. Kalinowski J. Kegler C. Knauber T. Konietzny S. Kopp M. Krause L. Krug D. Linke B. Mahmud T. Martinez-Arias R. McHardy A.C. Merai M. Meyer F. Mormann S. Muñoz-Dorado J. Perez J. Pradella S. Rachid S. Raddatz G. Rosenau F. Rückert C. Sasse F. Scharfe M. Schuster S.C. Suen G. Treuner-Lange A. Velicer G.J. Vorhölter F.J. Weissman K.J. Welch R.D. Wenzel S.C. Whitworth D.E. Wilhelm S. Wittmann C. Blöcker H. Pühler A. Müller R. Complete genome sequence of the myxobacterium Sorangium cellulosum. Nat. Biotechnol. 2007 25 11 1281 1289 10.1038/nbt1354 17965706
    [Google Scholar]
  180. Gregory K. Salvador L.A. Akbar S. Adaikpoh B.I. Stevens D.C. Survey of biosynthetic gene clusters from sequenced myxobacteria reveals unexplored biosynthetic potential. Microorganisms 2019 7 6 181 10.3390/microorganisms7060181 31238501
    [Google Scholar]
  181. Hoffmann T. Krug D. Bozkurt N. Duddela S. Jansen R. Garcia R. Correlating chemical diversity with taxonomic distance for discovery of natural products in myxobacteria. Nat. Commun. 2018 9 1 803 10.1038/s41467‑018‑03184‑1
    [Google Scholar]
  182. Amiri Moghaddam J. Crüsemann M. Alanjary M. Harms H. Dávila-Céspedes A. Blom J. Poehlein A. Ziemert N. König G.M. Schäberle T.F. Analysis of the genome and metabolome of marine myxobacteria reveals high potential for biosynthesis of novel specialized metabolites. Sci. Rep. 2018 8 1 16600 10.1038/s41598‑018‑34954‑y 30413766
    [Google Scholar]
  183. Ahearne A. Albataineh H. Dowd S.E. Stevens D.C. Assessment of evolutionary relationships for prioritization of myxobacteria for natural product discovery. Microorganisms 2021 9 7 1376 10.3390/microorganisms9071376 34202719
    [Google Scholar]
  184. Wenzel S.C. Müller R. The impact of genomics on the exploitation of the myxobacterial secondary metabolome. Nat. Prod. Rep. 2009 26 11 1385 1407 10.1039/b817073h 19844638
    [Google Scholar]
  185. Wenzel S.C. Müller R. Myxobacteria—‘microbial factories’ for the production of bioactive secondary metabolites. Mol. Biosyst. 2009 5 6 567 574 10.1039/b901287g 19462013
    [Google Scholar]
  186. Surup F. Viehrig K. Rachid S. Plaza A. Maurer C.K. Hartmann R.W. Müller R. Crocadepsins—depsipeptides from the myxobacterium Chondromyces crocatus found by a genome mining approach. ACS Chem. Biol. 2018 13 1 267 272 10.1021/acschembio.7b00900 29220569
    [Google Scholar]
  187. Panter F. Bader C.D. Müller R. The sandarazols are cryptic and structurally unique plasmid‐encoded toxins from a rare myxobacterium. Angew. Chem. Int. Ed. Engl. 2021 60 15 8081 8088 10.1002/anie.202014671
    [Google Scholar]
  188. Panter F. Krug D. Baumann S. Müller R. Self-resistance guided genome mining uncovers new topoisomerase inhibitors from myxobacteria. Chem. Sci. (Camb.) 2018 9 21 4898 4908 10.1039/C8SC01325J 29910943
    [Google Scholar]
  189. Peng-fei L. Shu-guang L. Zhi-feng L. Co-cultivation of Sorangium cellulosum strains affects cellular growth and biosynthesis of secondary metabolite epothilones. FEMS Microbiol. Ecol. 2013 85 2 358 368 10.1111/1574‑6941.12125
    [Google Scholar]
  190. Schäberle T.F. Orland A. König G.M. Enhanced production of undecylprodigiosin in Streptomyces coelicolor by co-cultivation with the corallopyronin A-producing myxobacterium, Corallococcus coralloides. Biotechnol. Lett. 2014 36 3 641 648 10.1007/s10529‑013‑1406‑0 24249103
    [Google Scholar]
  191. Kim J.H. Lee N. Hwang S. Kim W. Lee Y. Cho S. Palsson B.O. Cho B.K. Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture. J. Ind. Microbiol. Biotechnol. 2021 48 3-4 kuaa001 10.1093/jimb/kuaa001 33825906
    [Google Scholar]
  192. Yue X. Sheng D. Zhuo L. Li Y.Z. Genetic manipulation and tools in myxobacteria for the exploitation of secondary metabolism. Engineering Microbiology 2023 3 2 100075 10.1016/j.engmic.2023.100075 39629250
    [Google Scholar]
  193. Wang C.Y. Hu J.Q. Wang D.G. Li Y.Z. Wu C. Recent advances in discovery and biosynthesis of natural products from myxobacteria: An overview from 2017 to 2023. Nat. Prod. Rep. 2024 41 6 905 934 10.1039/D3NP00062A 38390645
    [Google Scholar]
  194. Karim M.D. Abuhena M. Rahman L. Leveraging CRISPR/Cas9 in notable bacteria for the production of industrially valuable compounds. In: Syst. Microbiol. Biomanufact 2025 5 2 1 9 10.1007/s43393‑024‑00326‑z
    [Google Scholar]
  195. Peng R. Wang Y. CRISPR/dCas9-mediated transcriptional improvement of the biosynthetic gene cluster for the epothilone production in Myxococcus xanthus. Microb. Cell Fact. 2018 17 15 10.1186/s12934‑018‑0867‑1
    [Google Scholar]
  196. Ye W. Liu T. Zhu M. Zhang W. Huang Z. Li S. Li H. Kong Y. Chen Y. An easy and efficient strategy for the enhancement of epothilone production mediated by TALE-TF and CRISPR/dcas9 systems in Sorangium cellulosum. Front. Bioeng. Biotechnol. 2019 7 334 10.3389/fbioe.2019.00334 32039165
    [Google Scholar]
  197. Hu W. Yang J. Wang J. Characteristics and immune functions of the endogenous CRISPR-Cas systems in myxobacteria. ASM J. 2024 9 6 1 8 10.1128/msystems.01210‑23
    [Google Scholar]
  198. Hu W. Wang Y. Yue X. An upgraded Myxococcus xanthus chassis with enhanced growth characteristics for efficient genetic manipulation. Eng. Microbiol. 2024 4 3 100155 10.1016/j.engmic.2024.100155
    [Google Scholar]
  199. Plaza A. Garcia R. Bifulco G. Martinez J.P. Hüttel S. Sasse F. Meyerhans A. Stadler M. Müller R. Aetheramides A and B, potent HIV-inhibitory depsipeptides from a myxobacterium of the new genus “Aetherobacter”. Org. Lett. 2012 14 11 2854 2857 10.1021/ol3011002 22616796
    [Google Scholar]
  200. Steinmetz H. Li J. Fu C. Zaburannyi N. Kunze B. Harmrolfs K. Schmitt V. Herrmann J. Reichenbach H. Höfle G. Kalesse M. Müller R. Isolation, structure elucidation, and (Bio)synthesis of haprolid, a cell‐type‐specific myxobacterial cytotoxin. Angew. Chem. Int. Ed. 2016 55 34 10113 10117 10.1002/anie.201603288 27404448
    [Google Scholar]
  201. Kunze B. Jansen R. Sasse F. Höfle G. Reichenbach H. Apicularens A and B, new cytostatic macrolides from Chondromyces species (myxobacteria): Production, physico-chemical and biological properties. J. Antibiot. 1998 51 12 1075 1080 10.7164/antibiotics.51.1075 10048565
    [Google Scholar]
  202. Raju R. Mohr K.I. Bernecker S. Herrmann J. Müller R. Cystodienoic acid: A new diterpene isolated from the myxobacterium Cystobacter sp. J. Antibiot. 2015 68 7 473 475 10.1038/ja.2015.8 25690355
    [Google Scholar]
  203. Kirsch V.C. Orgler C. Braig S. Jeremias I. Auerbach D. Müller R. Vollmar A.M. Sieber S.A. The cytotoxic natural product vioprolide A targets nucleolar protein 14, which is essential for ribosome biogenesis. Angew. Chem. Int. Ed. 2020 59 4 1595 1600 10.1002/anie.201911158 31658409
    [Google Scholar]
  204. Sun Y. Tomura T. Sato J. Iizuka T. Fudou R. Ojika M. Isolation and biosynthetic analysis of haliamide, a new pks-nrps hybrid metabolite from the marine myxobacterium haliangium ochraceum. Molecules 2016 21 1 59 10.3390/molecules21010059 26751435
    [Google Scholar]
  205. Fudou R. Iizuka T. Yamanaka S. Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium. 1. Fermentation and biological characteristics. J. Antibiot. 2001 54 2 149 152 10.7164/antibiotics.54.149 11302487
    [Google Scholar]
  206. Nadmid S. Plaza A. Lauro G. Garcia R. Bifulco G. Müller R. Hyalachelins A-C, unusual siderophores isolated from the terrestrial myxobacterium Hyalangium minutum. Org. Lett. 2014 16 16 4130 4133 10.1021/ol501826a 25058569
    [Google Scholar]
  207. Okanya P.W. Mohr K.I. Gerth K. Steinmetz H. Huch V. Jansen R. Müller R. Hyaladione, an S-methyl cyclohexadiene-dione from Hyalangium minutum. J. Nat. Prod. 2012 75 4 768 770 10.1021/np200776v 22497473
    [Google Scholar]
  208. Okoth D.A. Hug J.J. Garcia R. Müller R. Discovery, biosynthesis and biological activity of a succinylated myxochelin from the myxobacterial strain MSr12020. Microorganisms 2022 10 10 1959 10.3390/microorganisms10101959 36296235
    [Google Scholar]
  209. Zhang S. Menche D. Zahler S. Vollmar A.M. Liebl J. Förster F. In vitro anti-cancer effects of the actin-binding natural compound rhizopodin. Pharmazie 2015 70 9 610 615 [PMID: 26492647
    [Google Scholar]
  210. Jansen R. Sood S. Mohr K.I. Kunze B. Irschik H. Stadler M. Müller R. Nannozinones and sorazinones, unprecedented pyrazinones from myxobacteria. J. Nat. Prod. 2014 77 11 2545 2552 10.1021/np500632c 25397992
    [Google Scholar]
  211. Jansen R. Mohr K.I. Bernecker S. Stadler M. Müller R. Indothiazinone, an indolyl thiazolyl ketone from a novel myxobacterium belonging to the Sorangiineae. J. Nat. Prod. 2014 77 4 1054 1060 10.1021/np500144t 24697522
    [Google Scholar]
  212. Okanya P.W. Mohr K.I. Gerth K. Jansen R. Müller R. Marinoquinolines A-F, pyrroloquinolines from Ohtaekwangia kribbensis (Bacteroidetes). J. Nat. Prod. 2011 74 4 603 608 10.1021/np100625a 21456549
    [Google Scholar]
  213. Oka M. Nishiyama Y. Ohta S. Kamei H. Konishi M. Miyaki T. Glidobactins A. B and C, new antitumor antibiotics. I. Production, isolation, chemical properties and biological activity. J. Antibiot. 1998 41 10 1331 1337 10.7164/antibiotics.41.1331
    [Google Scholar]
  214. Schieferdecker S. König S. Koeberle A. Dahse H.M. Werz O. Nett M. Myxochelins target human 5-lipoxygenase. J. Nat. Prod. 2015 78 2 335 338 10.1021/np500909b 25686392
    [Google Scholar]
  215. Kjaerulff L. Raju R. Panter F. Scheid U. Garcia R. Herrmann J. Müller R. Pyxipyrrolones: Structure elucidation and biosynthesis of cytotoxic myxobacterial metabolites. Angew. Chem. Int. Ed. 2017 56 32 9614 9618 10.1002/anie.201704790 28590072
    [Google Scholar]
  216. Ricca M. Rizzacasa M.A. Chemistry and biology of spiroacetals from myxobacteria. Org. Biomol. Chem. 2021 19 13 2871 2890 10.1039/D1OB00026H 33683270
    [Google Scholar]
  217. Irschik H. Washausen P. Sasse F. Fohrer J. Huch V. Müller R. Prusov E.V. Isolation, structure elucidation, and biological activity of maltepolides: Remarkable macrolides from Myxobacteria. Angew. Chem. Int. Ed. 2013 52 20 5402 5405 10.1002/anie.201210113 23592574
    [Google Scholar]
  218. Höfle G. Gerth K. Reichenbach H. Kunze B. Sasse F. Forche E. Prusov E.V. Isolation, biological activity evaluation, structure elucidation, and total synthesis of eliamid: A novel complex I inhibitor. Chemistry 2012 18 36 11362 11370 10.1002/chem.201201879 22890974
    [Google Scholar]
  219. Jahns C. Hoffmann T. Müller S. Gerth K. Washausen P. Höfle G. Reichenbach H. Kalesse M. Müller R. Pellasoren: Structure elucidation, biosynthesis, and total synthesis of a cytotoxic secondary metabolite from Sorangium cellulosum. Angew. Chem. Int. Ed. 2012 51 21 5239 5243 10.1002/anie.201200327 22488911
    [Google Scholar]
  220. Sakaushi S. Nishida K. Fukada T. Senda-Murata K. Oka S. Sugimoto K. Differential responses of mitotic spindle pole formation to microtubule-stabilizing agents epothilones A and B at low concentrations. Cell Cycle 2008 7 4 477 483 10.4161/cc.7.4.5313 18235240
    [Google Scholar]
  221. Diestel R. Irschik H. Jansen R. Khalil M.W. Reichenbach H. Sasse F. Chivosazoles A and F, cytostatic macrolides from myxobacteria, interfere with actin. ChemBioChem 2009 10 18 2900 2903 10.1002/cbic.200900562 19852013
    [Google Scholar]
  222. Li X.W. Herrmann J. Zang Y. Grellier P. Prado S. Müller R. Nay B. Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues. Beilstein J. Org. Chem. 2013 9 1551 1558 10.3762/bjoc.9.176 23946854
    [Google Scholar]
  223. Horstmann N. Essig S. Bockelmann S. Wieczorek H. Huss M. Sasse F. Menche D. Archazolid A-15-O-β-D-glucopyranoside and iso-archazolid B: Potent V-ATPase inhibitory polyketides from the myxobacteria Cystobacter violaceus and Archangium gephyra. J. Nat. Prod. 2011 74 5 1100 1105 10.1021/np200036v 21513292
    [Google Scholar]
  224. Sarabia F. Martín-Gálvez F. García-Ruiz C. Sánchez-Ruiz A. Vivar-García C. Epi-, epoxy-, and C2-modified bengamides: Synthesis and biological evaluation. J. Org. Chem. 2013 78 11 5239 5253 10.1021/jo4003272 23647394
    [Google Scholar]
  225. Tannert R. Milroy L.G. Ellinger B. Hu T.S. Arndt H.D. Waldmann H. Synthesis and structure-activity correlation of natural-product inspired cyclodepsipeptides stabilizing F-actin. J. Am. Chem. Soc. 2010 132 9 3063 3077 10.1021/ja9095126 20148556
    [Google Scholar]
  226. Becker D. Kazmaier U. Synthesis and biological evaluation of dichlorinated chondramide derivatives. Eur. J. Org. Chem. 2015 2015 19 4198 4213 10.1002/ejoc.201500369
    [Google Scholar]
  227. Altmann K. Recent developments in the chemical biology of epothilones. Curr. Pharm. Des. 2005 11 13 1595 1613 10.2174/1381612053764715 15892665
    [Google Scholar]
  228. Lee F.Y.F. Borzilleri R. Fairchild C.R. Kim S.H. Long B.H. Reventos-Suarez C. Vite G.D. Rose W.C. Kramer R.A. BMS-247550: A novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin. Cancer Res. 2001 7 5 1429 1437 [PMID: 11350914
    [Google Scholar]
  229. Nicolaou K.C. Winssinger N. Pastor J. Ninkovic S. Sarabia F. He Y. Vourloumis D. Yang Z. Li T. Giannakakou P. Hamel E. Synthesis of epothilones A and B in solid and solution phase. Nature 1997 387 6630 268 272 10.1038/387268a0 9153390
    [Google Scholar]
  230. Chou T.C. Zhang X.G. Harris C.R. Kuduk S.D. Balog A. Savin K.A. Bertino J.R. Danishefsky S.J. Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. Proc. Natl. Acad. Sci. USA 1998 95 26 15798 15802 10.1073/pnas.95.26.15798 9861050
    [Google Scholar]
  231. Kowalski R.J. Giannakakou P. Hamel E. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol(R)). J. Biol. Chem. 1997 272 4 2534 2541 10.1074/jbc.272.4.2534 8999970
    [Google Scholar]
  232. Mok T.S.K. Choi E. Yau D. Johri A. Yeo W. Chan A.T.C. Wong C. Effects of patupilone (epothilone B; EPO906), a novel chemotherapeutic agent, in hepatocellular carcinoma: An in vitro study. Oncology 2006 71 3-4 292 296 10.1159/000106450 17657173
    [Google Scholar]
  233. Li F. Huang T. Tang Y. Li Q. Wang J. Cheng X. Utidelone inhibits growth of colorectal cancer cells through ROS/JNK signaling pathway. Cell Death Dis. 2021 12 338 10.1038/s41419‑021‑03619‑6
    [Google Scholar]
  234. Kappler S. Karmann L. Prudel C. Herrmann J. Caddeu G. Müller R. Vollmar A.M. Zahler S. Kazmaier U. Synthesis and biological evaluation of modified miuraenamides. Eur. J. Org. Chem. 2018 2018 48 6952 6965 10.1002/ejoc.201801391
    [Google Scholar]
  235. Liu Q. Yang X. Ji J. Zhang S.L. He Y. Novel nannocystin A analogues as anticancer therapeutics: Synthesis, biological evaluations and structure–activity relationship studies. Eur. J. Med. Chem. 2019 170 99 111 10.1016/j.ejmech.2019.03.011 30878835
    [Google Scholar]
  236. Tian Y. Wang J. Liu W. Yuan X. Tang Y. Li J. Chen Y. Zhang W. Stereodivergent total synthesis of Br-nannocystins underpinning the polyketide (10R,11S) configuration as a key determinant of potency. J. Mol. Struct. 2019 1181 568 578 10.1016/j.molstruc.2018.12.107
    [Google Scholar]
  237. Tian Y. Ding Y. Xu X. Bai Y. Tang Y. Hao X. Zhang W. Chen Y. Total synthesis and biological evaluation of nannocystin analogues modified at the polyketide phenyl moiety. Tetrahedron Lett. 2018 59 33 3206 3209 10.1016/j.tetlet.2018.07.028
    [Google Scholar]
  238. Okoth D.A. Hug J.J. Garcia R. Müller R. Three new stigmatellin derivatives reveal biosynthetic insights of its side chain decoration. Molecules 2022 27 14 4656. https://www.mdpi.com/1420-3049/27/14/4656/htm 10.3390/molecules2714465635889529
    [Google Scholar]
  239. Drača D. Mijatović S. Krajnović T. Pristov J.B. Đukić T. Kaluđerović G.N. Wessjohann L.A. Maksimović-Ivanić D. The synthetic tubulysin derivative, tubugi-1, improves the innate immune response by macrophage polarization in addition to its direct cytotoxic effects in a murine melanoma model. Exp. Cell. Res. 2019 380 2 159 170 https://linkinghub.elsevier.com/retrieve/pii/S0014482719302125 10.1016/j.yexcr.2019.04.028 31042500
    [Google Scholar]
  240. Shao M. Bai X. Ma X. Yan N. Yao L. Synthesis and antitumor activities of 3-substituted-analine derivatives: structure modifications of Tuv part of tubulysins. Chem. Cent. J. 2018 12 1 115 10.1186/s13065‑018‑0483‑5 30443866
    [Google Scholar]
  241. Nicolaou K.C. Erande R.D. Yin J. Vourloumis D. Aujay M. Sandoval J. Munneke S. Gavrilyuk J. Improved total synthesis of tubulysins and design, synthesis, and biological evaluation of new tubulysins with highly potent cytotoxicities against cancer cells as potential payloads for antibody–drug conjugates. J. Am. Chem. Soc. 2018 140 10 3690 3711 10.1021/jacs.7b12692 29381062
    [Google Scholar]
  242. Lazzari P. Spiga M. Sani M. Zanda M. Fleming I.N. KEMTUB012-NI2, a novel potent tubulysin analog that selectively targets hypoxic cancer cells and is potentiated by cytochrome p450 reductase downregulation. Hypoxia 2017 5 45 59 10.2147/HP.S132832 28580362
    [Google Scholar]
  243. Le H.V. Van Le H. Van Tran L. Tran A.T. Thi T. Tran P. Letter synlett design, synthesis, and cytotoxic activity of new tubulysin analogues H N N O OAc. Synlett 2021 2022 187 195
    [Google Scholar]
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Anticancer Compounds from Myxobacteria: Current Scenario and Future Perspectives
Bentham Science Publishers ; https://doi.org/10.2174/0118715206384510250625004749
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  • Article Type:     Review Article
Keywords: natural products ; myxobacteria ; secondary metabolites ; analogs ; Anti-cancer compounds ; biosynthetic gene clusters ; genome mining

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