Shedding light on Paraconiothyrium brasiliense: Secondary metabolites, biological activities, and computational studies

Sabrin R. M. Ibrahim Abdulrahim A. Alzain Fatima A. Elbadwi Abdulrahman E. Koshak Aram Hamad AlSaedi Ahmed Ashour Wadah Osman Ikhlas A. Sindi Selwan M. El-Sayed Abdelbasset A. Farahat Ahmed H.E. Hassan Gamal A. Mohamed   

Open Access   

Published:  May 24, 2024

DOI: 10.7324/JAPS.2024.184503

Fungi are renowned as a prolific source for the biosynthesis of therapeutically valuable metabolites. Paraconiothyrium genus (Leptosphaeriaceae) demonstrates remarkable potential for the biosynthesis of a wide array of metabolites, including macrolides, terpenoids, polyketides, phenolics, and furanones, which exhibit diverse bioactivities. The present review focused on the reported metabolites derived from Paraconiothyrium brasiliense, including their chemical structures and bioactive properties. Furthermore, it delves into the elucidation of the biosynthetic pathways for  these metabolites. This review encompasses the description of over 92 compounds reported in the literature from 2010 to October 2023. In addition, in silico studies may explain the potential mechanisms underlying the neuroprotective properties of certain furanone derivatives against central nervous system disorders. Among the tested compounds against KEAP1 through Keap1/Nrf2 pathway-mediated neuroprotection, paraconfuranone I (48), paraconfuranone (50), and paraconfuranone L (51) displayed docking scores ranging from −6.158 to −6.612 kcal/mol, similar to the exciting reference compound which achieved the highest docking score of −6.633 kcal/mol. Moreover, new potential activities of some compounds as inhibitors against the LasR target of Pseudomonas aeruginosa were elucidated using molecular docking and absorption, distribution, metabolism, excretion, and toxicity prediction. Specifically, 1-(1’,2’-dideoxy-α-D-nucleopyranosyl)-β-carboline (73) had the highest docking score at −11.327 kcal/mol, followed by 1-acetyl-β-carboline (75) at −10.055 kcal/mol, in comparison to reference compound (docking score −10.023 kcal/ mol). In addition, ten other compounds displayed competitive docking scores ranging from −9.813 to −9.312 kcal/ mol. This suggested the potential of P. brasiliense as a promising lead for antibacterial and neuroprotective agents.

Keyword:     Paraconiothyrium brasiliense secondary metabolites bioactivities sustainable development goals  life on land molecular docking ADMET prediction


Ibrahim SRM, Alzain AA, Elbadwi FA, Koshak AE, AlSaedi AH, Ashour A, Osman W, Sindi IA, El-Sayed SM, Farahat AA, Hassan AHE, Mohamed GA. Shedding light on Paraconiothyrium brasiliense: Secondary metabolites, biological activities, and computational studies. J Appl Pharm Sci, 2024. Online First.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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1. Ryan MJ, McCluskey K, Verkleij G, Robert V, Smith D. Fungal biological resources to support international development: challenges and opportunities. World J Microbiol Biotechnol. 2019;35:139.

2. Tennakoon DS, Thambugala KM, Silva NID, Suwannarach N, Lumyong S. A taxonomic assessment of novel and remarkable fungal species in Didymosphaeriaceae (Pleosporales, Dothideomycetes) from plant Litter. Front Microbiol. 2022;13:1016285.

3. Kržišnik D, Gonçalves J. Environmentally conscious technologies using fungi in a climate-changing world. Earth. 2023;4:69-77.

4. Purahong W, Pietsch KA, Lentendu G, Schöps R, Bruelheide H, Wirth C, et al. Characterization of unexplored deadwood mycobiome in highly diverse subtropical forests using culture-independent molecular technique. Front Microbiol. 2017;8:574.

5. Hareeri RH, Aldurdunji MM, Abdallah HM, Alqarni AA, Mohamed SG, Mohamed GA, et al. spergillus Ochraceus: metabolites, bioactivities, biosynthesis, and biotechnological potential. Molecules. 2022;27:6759.

6. Ibrahim SR, Sirwi A, Eid BG, Mohamed SG, Mohamed GA. Bright side of Fusarium Oxysporum: secondary metabolites bioactivities and industrial relevance in biotechnology and nanotechnology. J Fungi. 2021;7:943.

7. Ibrahim SR, Mohamed SG, Altyar AE, Mohamed GA. Natura products of the fungal genus umicola: diversity, biological activity, and industrial importance. Curr Microbiol. 2021;78:2488-509.

8. Saye LM, Navaratna TA, Chong JP, O'Malley MA, Theodorou MK, Reilly M. The Anaerobic fungi: challenges and opportunities for industrial lignocellulosic biofuel production. Microorganisms. 2021;9:694.

9. Ibrahim SRM, Choudhry H, Asseri AH, Elfaky MA, Mohamed SGA, Mohamed GA. Stachybotrys Chartarum-a hidden treasure: secondary metabolites, bioactivities, and biotechnological relevance. J Fungi. 2022;8:504.

10. Ibrahim SRM, Altyar AE, Mohamed SGA, Mohamed GA. Genus Thielavia: phytochemicals, ndustrial importance and biological relevance. Nat Prod Res. 2022;36:5108-23.

11. Ibrahim SR, Omar AM, Muhammad YA, Alqarni AA, Alshehri AM, Mohamed SG, et al. Advances in fungal phenaloenones-natural metabolites with great promise: biosynthesis, bioactivities, and an in silico evaluation of their potential as human glucose transporter 1 inhibitors. Molecules. 2022;27:6797.

12. Omar AM, Mohamed GA, Ibrahim SR. Chaetomugilins and chaetoviridins-promising natural metabolites: structures, separation, characterization, biosynthesis, bioactivities, molecular docking, and molecular dynamics. J Fungi. 2022;8:127.

13. Khayat MT, Mohammad KA, Omar AM, Mohamed GA, Ibrahim SR. Fungal bergamotane sesquiterpenoids-potential metabolites: sources, bioactivities, and biosynthesis. Mar Drugs. 2022;20:771.

14. Ibrahim SRM, Mohamed GA, Al Haidari RA, El-Kholy AA, Zayed MF, Khayat MT. Biologically active fungal depsidones: chemistry, biosynthesis, structural characterization, and bioactivities. Fitoterapia. 2018;129:317-65.

15. Prescott TA, Hill R, Mas-Claret E, Gaya E, Burns E. Fungal drug discovery for chronic disease: history, new discoveries and new approaches. Biomolecules. 2013;13:986.

16. Li H, Chen L, Xiong X, Yang H, Xu B, Liu C, et al. Structural elucidation and nuclear magnetic resonance spectral assignments of five new compounds from Paraconiothyrium brasiliense. Magn Reson Chem. 2013;61:184-92.

17. Verkley G, Dukik K, Renfurm R, Göker M, Stielow JB. Novel genera and species of coniothyrium-like fungi in montagnulaceae (Ascomycota). Persoonia. 2014;32:25-51.

18. Verkley GJ, da Silva M, Wicklow DT, Crous PW. Paraconiothyrium, a new genus to accommodate the mycoparasite Coniothyrium minitans, Anamorphs of paraphaeosphaeria, and four new species. Stud Mycol. 2004;50:323-5.

19. Arredondo-Santoyo M, Vázquez-Garcidueñas MS, Vázquez- Marrufo G. Identification and haracterization of the biotechnological potential of a wild strain of Paraconiothyrium sp. Biotechnol Prog. 2018;34:846-57.

20. Xu G, Mi J, Yang T, Wu L, Yuan X, Li G. Two new polyketide metabolites isolated from araconiothyrium brasiliense. Chem Nat Compd. 2017;53:870-73.

21. Colombier M, Alanio A, Denis B, Melica G, Garcia-Hermoso D, Levy B, et al. Dual invasive infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a renal transplant recipient: case report and comprehensive review of the literature of Phaeoacremonium Phaeohyphomycosis. J Clin Microbiol. 2015;53:2084-94.

22. Wang W, Shi Y, Liu Y, Zhang Y, Wu J, Zhang G, et al. Brasilterpenes A-E, bergamotane sesquiterpenoid derivatives with hypoglycemic activity from the deep sea-derived fungus Paraconiothyrium brasiliense HDN15-135. Mar Drugs. 2022;20:338.

23. Afshan NUS, Mujahid U, Ishaq A, Khalid AN. First report of leaf spot of Sarcococca Saligna caused by Paraconiothyrium brasiliense in Pakistan. J Plant Pathol. 2020;102:561.

24. Liu H, Zhang Y, Chen J. Whole-Genome sequencing and functional annotation of pathogenic Paraconiothyrium brasiliense causing human cellulitis. Hum Genomics. 2013;17:65.

25. Liu L, Gao H, Chen X, Cai X, Yang L, Guo L, et al. Brasilamides A-D: sesquiterpenoids from the plant endophytic fungus Paraconiothyrium brasiliense . Eur J Org Chem. 2010;2010:3302-6.

26. Guo Z, Ren F, Che Y, Liu G, Liu L. New bergamotane sesquiterpenoids from the plant endophytic fungus Paraconiothyrium brasiliense. Molecules. 2015;20:14611-20.

27. Wang W, Shi Y, Liu Y, Zhang Y, Wu J, Zhang G. et al. Brasilterpenes A-E, bergamotane sesquiterpenoid derivatives with hypoglycemic activity from the deep sea-derived fungus Paraconiothyrium brasiliense HDN15-135. Mar Drugs. 2022;20:338.

28. Nakashima K, Tomida J, Hirai T, Kawamura Y, Inoue M. Paraconiothins A-J: sesquiterpenoids from the endophytic fungus Paraconiothyrium brasiliense ECN258. J Nat Prod. 2019;82:3347- 56.

29. Liu C, Wang L, Chen J, Guo Z, Tu X, Deng Z, et al. Paraconfuranones A-H, eight new furanone analogs from the insect-associated fungus Paraconiothyrium brasiliense MZ-1. Magn Reson Chem. 2015;53:317-22.

30. Liu C, Yu X, Guo Z, He H, Tu X, Deng Z, et al. Structural elucidation and NMR spectral assignments of paraconfuranones I-M from the insect-associated fungus Paraconiothyrium brasiliense. Magn Reson Chem. 2016;54:916-21.

31. Ji-Hui Z, Xin-Lei Y, Meng T, Hui LI, Zhao-Xia L, Cheng-Xiong L, et al. Study on β-carboline alkaloids produced by endophytic fungus Paraconiothyrium brasiliense and their xanthine oxidase inhibitory activity. Nat Prod Res Develop. 2021;33:41.

32. Sathiyaseelan A, Saravanakumar K, Mariadoss AVA, Kim KM, Wang M. Antibacterial activity of ethyl acetate extract of endophytic fungus (Paraconiothyrium brasiliense) through targeting dihydropteroate synthase (DHPS). Process Biochem. 2021;111:27-35.

33. Liu L, Chen X, Li D, Zhang Y, Li L, Guo L, et al. Bisabolane sesquiterpenoids from the plant ndophytic fungus Paraconiothyrium brasiliense. J Nat Prod. 2015;78:746-53.

34. Zhang Y, Zhang Z, Wang B, Liu L, Che Y. Design and synthesis of natural product derivatives with selective and improved cytotoxicity based on a sesquiterpene scaffold. Bioorg Med Chem Lett. 2016;26:1885-8.

35. Sathiyaseelan A, Saravanakumar K, Naveen KV, Han, K, Zhang X, Jeong MS, et al. Combination of Paraconiothyrium brasiliense fabricated titanium dioxide nanoparticle and antibiotics enhanced antibacterial and antibiofilm properties: a Toxicity Evaluation. Environ Res. 2022;212:113237.

36. Garyali S, Kumar A, Reddy MS. Diversity and antimitotic activity of taxol-producing endophytic fungi isolated from Himalayan Yew. Ann. Microbiol. 2014;64:1413-22.

37. Shasmita NRS, Rath SK, Behera S, Naik SK. In vitro secondary metabolite production through fungal elicitation: an Approachfor sustainability. Singapore: Fungal Nanobionics: Principles and Applications, Springer; 2018, pp 215-42.

38. Salehi M, Moieni A, Safaie N, Farhadi S. Elicitors derived from endophytic fungi Chaetomium globosum and Paraconiothyrium brasiliense enhance paclitaxel production in Corylus Avellana cell suspension culture. Plant Cell Tiss. Organ Cult. 2019;136:161-71.

39. Choi MA, Park SJ, Ahn GR, Kim, SH. Identification and characterization of Paraconiothyrium brasiliense from garden plant Pachysandra Terminalis. Kor J Mycol. 2014;42:262-68.

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