| ORIGINAL ARTICLES |
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New sesquiterpenoids with anti-inflammatory effects from phytopathogenic fungus Bipolaris sorokiniana 11134 |
| Qiang Yin1, Jianying Han1,2,3, Guixiang Yang1, Zhijun Song4, Keke Zou1, Kangjie Lv1, Zexu Lin1, Lei Ma1, Miaomiao Liu2, Yunjiang Feng2, Ronald J. Quinn2, Tom Hsiang5, Lixin Zhang1, Xueting Liu1, Guoliang Zhu1, Jingyu Zhang1 |
1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China;
2. Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, Australia;
3. Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD, 4072, Australia;
4. Chinese Academy of Sciences, Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China;
5. School of Environmental Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada |
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Abstract Sesquiterpenoids represent a structurally diverse class of natural products widely recognized for their ecological significance and pharmacological potential, including antimicrobial, anti-inflammatory, and anticancer properties. As part of our efforts to explore bioactive secondary metabolites from phytopathogenic fungi, we conducted a molecular networking-based analysis of Bipolaris sorokiniana isolate BS11134, which was fermented on a rice medium. This analysis led to the identification of three new seco-sativene-type sesquiterpenoids (1-3) and seven known analogues (4-10), with the NMR data of compound 4 being reported for the first time. The structures of these compounds were elucidated using HR-ESI-MS and extensive spectroscopic data analysis. Notably, compound 9 significantly inhibited nitrous oxide expression in lipopolysaccharide (LPS)-treated RAW264.7 cells in vitro (inhibition rate: 84.7±1.7% at 10 μM), while compound 1 (10 μM) showed a weak inhibitory effect (inhibition rate=28.0±2.4%). Additionally, we proposed a biosynthetic pathway for these compounds. This study not only expands the chemical space of the helminthoporene class of molecules but also underscores the untapped potential of phytopathogenic fungi as promising sources of structurally unique and biologically active natural products.
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| Keywords
Phytopathogenic fungi
Bipolaris sorokiniana 11134
Sesquiterpenoid
Anti-inflammatory
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| Fund:This study was funded by National Key Research and Development Program of China (2019YFA0906200, 2020YFA0907200); National Natural Science Foundation of China (31430002, 31720103901, 32121005, 21977029); Shanghai Rising-Star Program (20QA1402800); Open Project Funding of the State Key Laboratory of Bioreactor Engineering (B18022); Shanghai Science and Technology Commission (18 JC1411900); Shanghai Sci-Tech Inno Center for Infection & Immunity (SSIII-2024 A02). |
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Issue Date: 18 June 2025
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1. Berenbaum F. Proinflammatory cytokines, prostaglandins, and the chondrocyte: mechanisms of intracellular activation. Joint Bone Spine. 2000;67(6):561-4. https://doi.org/10.1016/S1297-319X(00)00212-8.
2. Reddy DB, Reddanna P. Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages. Biochem Biophys Res Commun. 2009;381(1):112-7. https://doi.org/10.1016/j.bbrc.2009.02.022.
3. Salminen A, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Inflammation in Alzheimer’s disease: amyloid-β oligomers trigger innate immunity defence via pattern recognition receptors. Prog Neurobiol. 2009;87(3):181-94. https://doi.org/10.1016/j.pneurobio.2009.01.001.
4. Shah IM, Macrae IM, Di Napoli M. Neuroinflammation and neuroprotective strategies in acute ischaemic stroke—from bench to bedside. Curr Mol Med. 2009;9(3):336-54. https://doi.org/10.2174/156652409787847236.
5. J B. Dictionary of natural products on CD-ROM. Version 101; 2002.
6. Hana B, Veronika H, Lenka S, Martin A, Iva B. Antioxidant, pro-oxidant and other biological activities of sesquiterpenes. Curr Top Med Chem. 2014;14(22):2478-94. https://doi.org/10.2174/1568026614666141203120833.
7. Jesus Duran-Pena M, Botubol Ares JM, Hanson JR, Collado IG, Hernandez-Galan R. Biological activity of natural sesquiterpenoids containing a gem-dimethylcyclopropane unit. Nat Prod Rep. 2015;32(8):1236-48. https://doi.org/10.1039/c5np00024f.
8. Elissawy AM, El-Shazly M, Ebada SS, Singab AB, Proksch P. Bioactive terpenes from marine-derived fungi. Mar Drugs. 2015;13(4):1966-92. https://doi.org/10.3390/md13041966.
9. Gliszczynska A, Brodelius PE. Sesquiterpene coumarins. Phytochem Rev. 2012;11(1):77-96. https://doi.org/10.1007/s11101-011-9220-6.
10. Orofino Kreuger MR, Grootjans S, Biavatti MW, Vandenabeele P, Dherde K. Sesquiterpene lactones as drugs with multiple targets in cancer treatment: focus on parthenolide. Anticancer Drugs. 2012;23(9):883-96. https://doi.org/10.1097/CAD.0b013e328356cad9.
11. Spivey AC, Weston M, Woodhead S. Celastraceae sesquiterpenoids: biological activity and synthesis. Chem Soc Rev. 2002;31(1):43-59. https://doi.org/10.1039/b000678p.
12. Tanasova M, Sturla SJ. Chemistry and biology of acylfulvenes: sesquiterpene-derived antitumor agents. Chem Rev. 2012;112(6):3578-610. https://doi.org/10.1021/cr2001367.
13. Yang X-L, Zhang J-Z, Luo D-Q. The taxonomy, biology and chemistry of the fungal Pestalotiopsis genus. Nat Prod Rep. 2012;29(6):622-41. https://doi.org/10.1039/c2np00073c.
14. Abraham WR. Bioactive sesquiterpenes produced by fungi: are they useful for humans as well? Curr Med Chem. 2001;8(6):583-606. https://doi.org/10.2174/0929867013373147.
15. Kramer R, Abraham W-R. Volatile sesquiterpenes from fungi: what are they good for? Phytochem Rev. 2012;11(1):15-37. https://doi.org/10.1007/s11101-011-9216-2.
16. Quinn RA, Nothias L-F, Vining O, Meehan M, Esquenazi E, Dorrestein PC. Molecular networking as a drug discovery, drug metabolism, and precision medicine strategy. Trends Pharmacol Sci. 2017;38(2):143-54. https://doi.org/10.1016/j.tips.2016.10.011.
17. Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y, et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat Biotechnol. 2016;34(8):828-37. https://doi.org/10.1038/nbt.3597.
18. Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD, et al. Mass spectral molecular networking of living microbial colonies. Proc Natl Acad Sci USA. 2012;109(26):E1743-52. https://doi.org/10.1073/pnas.1203689109.
19. Nothias L-F, Petras D, Schmid R, Duehrkop K, Rainer J, Sarvepalli A, et al. Feature-based molecular networking in the GNPS analysis environment. Nat Methods. 2020;17(9):905. https://doi.org/10.1038/s41592-020-0933-6.
20. Mayo PD, Spencer EY, White RW. Helminthosporal, the toxin from Helminthosporium sativum. I. Isolation and characterization. Can J Chem. 1961;39(8):1608-12. https://doi.org/10.1139/v61-205.
21. Gayed SK. Production of symptoms of barley leaf-spot disease by culture filtrate of Helminthosporium satirum. Nature. 1961;191(4789):725-6. https://doi.org/10.1038/191725b0.
22. Ludwig RA. Toxin production by Helminthosporium sativum P.K & B. and its significance in disease development. Can J Bot. 1957;35(3):291-303. https://doi.org/10.1139/b57-026.
23. Han J, Zhang J, Song Z, Liu M, Hu J, Hou C, et al. Genome- and MS-based mining of antibacterial chlorinated chromones and xanthones from the phytopathogenic fungus Bipolaris sorokiniana strain 11134. Appl Microbiol Biotechnol. 2019;103(13):5167-81. https://doi.org/10.1007/s00253-019-09821-z.
24. Wang J, Chitsaz F, Derbyshire MK, Gonzales NR, Gwadz M, Lu S, et al. The conserved domain database in 2023. Nucleic Acids Res. 2023;51(D1):D384-8. https://doi.org/10.1093/nar/gkac1096.
25. Blin K, Shaw S, Augustijn HE, Reitz ZL, Biermann F, Alanjary M, et al. antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation. Nucleic Acids Res. 2023;51(W1):W46-50. https://doi.org/10.1093/nar/gkad344.
26. Huaran Z, Haiyan Z, Yuqi H, Yi Z. Genome mining reveals the biosynthesis of sativene and its oxidative conversion to seco-sativene. Org Lett. 2024;26(1):338-43. https://doi.org/10.1021/acs.orglett.3c04005.
27. Abdel-Lateff A, Okino T, Alarif WM, Al-Lihaibi SS. Sesquiterpenes from the marine algicolous fungus Drechslera sp. J Saudi Chem Soc. 2013;17(2):161-5. https://doi.org/10.1016/j.jscs.2011.03.002.
28. Fan Y-Z, Tian C, Tong S-Y, Liu Q, Xu F, Shi B-B, et al. The antifungal properties of terpenoids from the endophytic fungus Bipolaris eleusines. Nat Prod Bioprospect. 2023;13(1):43. https://doi.org/10.1007/s13659-023-00407-x.
29. Osterhage C, König GM, Höller U, Wright AD. Rare sesquiterpenes from the algicolous fungus Drechslera dematioidea. J Nat Prod. 2002;65(3):306-13. https://doi.org/10.1021/np010092l.
30. Li Z-H, Ai H-L, Yang M-S, He J, Feng T. Bioactive sativene sesquiterpenoids from cultures of the endophytic fungus Bipolaris eleusines. Phytochem Lett. 2018;27:87-9. https://doi.org/10.1016/j.phytol.2018.07.007.
31. Grimblat N, Zanardi MM, Sarotti AM. Beyond DP4: an improved probability for the stereochemical assignment of isomeric compounds using quantum chemical calculations of NMR shifts. J Org Chem. 2015;80(24):12526-34. https://doi.org/10.1021/acs.joc.5b02396.
32. Zhang L, Liu X, Zhang J, Jiang L, Zhu G, Han J, et al. Preparation method of helminthosporol type sesquiterpenoids and its preparation method thereof. ZL201910566725X; 2019.
33. Tamura S, Sakurai A. Syntheses of several compounds related to helminthosporol and their plant growth-regulating activities. Agric Biol Chem. 2014;28(5):337-8. https://doi.org/10.1080/00021369.1964.10858247.
34. Nakajima H, Isomi K, Hamasaki T, Ichinoe M. Sorokinianin—a novel phytotoxin produced by the phytopathogenic fungus Bipolaris-sorokiniana. Tetrahedron Lett. 1994;35(51):9597-600. https://doi.org/10.1016/0040-4039(94)88520-6.
35. Lodewyk MW, Gutta P, Tantillo DJ. Computational studies on biosynthetic carbocation rearrangements leading to sativene, cyclosativene, α-ylangene, and β-ylangene. J Org Chem. 2008;73(17):6570-9. https://doi.org/10.1021/jo800868r.
36. Phan C-S, Li H, Kessler S, Solomon PS, Piggott AM, Chooi Y-H. Bipolenins K-N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana. Beilstein J Org Chem. 2019;15:2020-8. https://doi.org/10.3762/bjoc.15.198.
37. Nakajima H, Toratsu Y, Fujii Y, Ichinoe M, Hamasaki T. Biosynthesis of sorokinianin a phytotoxin of Bipolaris sorokiniana: evidence of mixed origin from the sesquiterpene and TCA pathways. Tetrahedron Lett. 1998;39(9):1013-6. https://doi.org/10.1016/S0040-4039(97)10803-6.
38. Steele CL, Crock J, Bohlmann J, Croteau R. Sesquiterpene synthases from grand fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of delta-selinene synthase and gamma-humulene synthase. J Biol Chem. 1998;273(4):2078-89. https://doi.org/10.1074/jbc.273.4.2078.
39. Elisashvili V. Submerged cultivation of medicinal mushrooms: bioprocesses and products (review). Int J Med Mushrooms. 2012;14(3):211-39. https://doi.org/10.1615/IntJMedMushr.v14.i3.10.
40. Ulrike L, Niedermeyer THJ, Wolf-Dieter J. The pharmacological potential of mushrooms. Evid Based Complement Altern Med. 2005;2(3):285-99. https://doi.org/10.1093/ecam/neh107.
41. Li Y-Y, Tan X-M, Yang J, Guo L-P, Ding G. Naturally occurring seco-sativene sesquiterpenoid: chemistry and biology. J Agric Food Chem. 2020;68(37):9827-38. https://doi.org/10.1021/acs.jafc.0c04560.
42. Jiang L, Zhang X, Sato Y, Zhu G, Minami A, Zhang W, et al. Genome-based discovery of enantiomeric pentacyclic sesterterpenes catalyzed by fungal bifunctional terpene synthases. Org Lett. 2021;23(12):4645-50. https://doi.org/10.1021/acs.orglett.1c01361.
43. Jiang L, Zhu G, Han J, Hou C, Zhang X, Wang Z, et al. Genome-guided investigation of anti-inflammatory sesterterpenoids with 5-15 trans-fused ring system from phytopathogenic fungi. Appl Microbiol Biotechnol. 2021;105(13):5407-17. https://doi.org/10.1007/s00253-021-11192-3.
44. Ruggeri FM, Frisch M, Trucks G, Schlegel H, Scuseria G, Robb M, et al. Gaussian 03, Revision E01; 2004.
45. Cammi R, Tomasi J. Remarks on the use of the apparent surface charges (ASC) methods in solvation problems: iterative versus matrix-inversion procedures and the renormalization of the apparent charges. J Comput Chem. 1995;16(12):1449-58. https://doi.org/10.1002/jcc.540161202.
46. Yang G-X, Ge S-L, Wu Y, Huang J, Li S-L, Wang R, et al. Design, synthesis and biological evaluation of 3-piperazinecarboxylate sarsasapogenin derivatives as potential multifunctional anti-Alzheimer agents. Eur J Med Chem. 2018;156:206-15. https://doi.org/10.1016/j.ejmech.2018.04.054. |
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