Chromatographic and mass spectroscopic guided discovery of Trichoderma peptaibiotics and their bioactivity

Abstract

Peptaibiotics are linear or cyclic peptide antibiotics characterized by the non-proteinogenic amino acid, alpha-aminoisobutyric acid. They exhibit a wide range of bioactivity against various pathogens. This report presents a comprehensive review of analytical methods for Trichoderma cultivation, production, isolation, screening, purification, and characterization of peptaibiotics, along with their bioactivity. Numerous techniques are currently available for each step, and we focus on describing the most commonly used and recently developed chromatographic and spectroscopic techniques. Investigating peptaibiotics requires efficient culture media, growth conditions, and isolation and purification techniques. The combination of chromatographic and spectroscopic tools offers a better opportunity for characterizing and identifying peptaibiotics. The evaluation of the chemical and biological properties of this compound has also been explored concerning its potential application in pharmaceutical and other industries. This review aims to summarize available data on the techniques and tools used to screen and purify peptaibiotics from Trichoderma fungi and bioactivity against various pathogens.

Keywords

Chromatography / peptaibiotics / spectroscopy / Trichoderma

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

CRediT authorship contribution statement

Adigo Setargie: Writing - original draft. Chen Wang: Writing - review & editing. Liwen Zhang: Supervision. Yuquan Xu: Supervision.

References

[1] I. Afzal, A. Sabir, S. Sikandar, Trichoderma:biodiversity, abundances, and biotech- nological applications, in: A.N. Yadav (Ed.), Recent Trends in Mycological Re- search, Fungal Biology, Springer, Cham, 2021 ch..

[2] P. Alfaro-Vargas, A. Bastos-Salas, R. Muñoz-Arrieta, R. Pereira-Reyes, M. Redondo-Solano, J. Fernández, A. Mora-Villalobos, J.P. López-Gómez, Peptaibol production and characterization from Trichoderma asperellum and their action as biofungi- cide, J. Fungi. 8 (10) (2022) 1037, doi:10.3390/jof8101037.

[3] I. Ali, V.D. Gaitonde, A. Grahn, Halo columns: new generation technology for high speed liquid chromatography, J. Chromatogr. Sci. 48 (5) (2010) 386-394, doi:10.1093/chromsci/48.5.386.

[4] B. Aslam, M. Basit, M.A. Nisar, M. Khurshid, M.H. Rasool, Proteomics: technolo- gies and their applications, J. Chromatogr. Sci. 18 (2016) 1-5, doi:10.1093/chrom-sci/bmw167.

[5] I. Augeven-Bour, S. Rebuffat, C. Auvin, C. Goulard, Y. Prigent, B. Bodo, Harzianin HB I, an 11-residue peptaibol from Trichoderma harzianum: isolation, sequence, solution synthesis and membrane activity, J. Chem. Soc. (10) (1997) 1587-1594, doi:10.1039/A605629F.

[6] C. Auvin-Guette, S. Rebuffat, Y. Prigent, B. Bodo, Trichogin A IV, an 11-residue lipopeptaibol from Trichoderma longibrachiatum, J. Am. Chem. Soc. 114 (6)(1992) 2170-2174, doi:10.1021/ja00032a035.

[7] C. Auvin-Guette, S. Rebuffat, I. Vuidepot, M. Massias, B. Bodo, Structural elucida- tion of trikoningins KA and KB, peptaibols from Trichoderma koningii, J. Chem. Soc. 1 (2) (1993) 249-255, doi:10.1039/P19930000249.

[8] D. Balázs, T. Marik, A. Szekeres, L.Kredics C.Vágvölgyi, Tyagi C, Structure-activity correlations for peptaibols obtained from clade Longibrachiatum of Trichoderma: A combined experimental and computational approach, Comput. Struct. Biotechnol. J. 21 (2023) 1860-1873, doi:10.1016/j.csbj.2023.02.046.

[9] M. Barber, R.S. Bordoli, R.D. Sedgwick, A.N. Tyler, Fast atom bombardment of solids as an ion source in mass spectrometry, Nature 293 (1981) 270-275, doi:10.1038/293270a0.

[10] E. Benedetti, B.Di Blasio A.Bavoso, V. Pavone, C. Pedone, C. Toniolo, G.M. Bonora, Peptaibol antibiotics: a study on the helical structure of the 2-9 sequence of emerimicins III and IV, Proc. Natl. Acad. Sci. U.S.A. 79 (24) (1982) 7951-7954, doi:10.1073/pnas.79.24.795.

[11] T. Benítez, A.M. Rincón, M.C. Limón, A.C. Codon, Biocontrol mechanisms of Tri- choderma strains, Int. microbiol. 7 (4) (2004) 249-260.

[12] A. Berg, B. Schlegel, W. Ihn, U. Demuth, U. Graefe, Isolation and structural eluci- dation of new peptaibols, bergofungins B, C and D, from Emericellopsis donezkii HKI 0059, J. Antibiot. 52 (7) (1999) 666-669, doi:10.7164/antibiotics.52.666.

[13] P. Biniarz, M. Ł ukaszewicz, T. Janek, Screening concepts, characterization and structural analysis of microbial-derived bioactive lipopeptides: a review, Crit. Rev. Biotechnol. 37 (3) (2017) 393-410, doi:10.3109/07388551.2016.1163324.

[14] I.M. Bird, High performance liquid chromatography: principles and clinical appli- cations, Br. Med. J. 299 (6702) (1989) 783, doi:10.1136/bmj.299.6702.783.

[15] D. Brewer, F.G. Mason, A. Taylor, The production of alamethicins by Trichoderma spp, Can. J. Microbiol. 33 (7) (1987) 619-625, doi:10.1139/m87-108.

[16] J.P. Brito, M.H. Ramada, M.T. de Magalhães, L.P. Silva, C.J. Ulhoa, Peptaibols from Trichoderma asperellum TR356 strain isolated from Brazilian soil, Springerplus 3 (1) (2014) 1-10, doi:10.1186/2193-1801-3-600.

[17] H. Brückner, H. Graf, Paracelsin, a peptide antibiotic containing 𝛼-aminoisobutyric acid, isolated from Trichoderma ressei Simmons Part A, Experientia 39 (1983) 528-530, doi:10.1007/BF01965190.

[18] H. Brückner, G. Jung, M. Przybylski, Chromatographic and mass spectrometric characterization of the structures of the polypeptide antibiotics samarosporin and stilbellin and identity with emerimicin, Chromatographia 17 (1983) 679-685, doi:10.1007/BF02259320.

[19] H. Brückner, M. Przybylski, Isolation and structural characterization of polypeptide antibiotics of the peptaibol class by high-performance liquid chromatography with field desorption and fast atom bombardment mass spectrometry, J. Chromatogr. A 296 (1984) 263-275, doi:10.1016/S0021-9673(01)96420-9.

[20] H. Brückner, W.A. König, M. Aydin, G. Jung, A40. Trichotoxin, Purifica- tion by counter-current distribution and sequencing of isolated fragments, Biochim. Biophys. Acta, Protein Struct. Mol. Enzymol. 827 (1) (1985) 51-62, doi:10.1016/0167-4838(85)90100-1.

[21] S.Zeilinger K. Brunner R. Ciliento S.L. Woo M. Lorito C.P. Kubicek R.L. Mach, Improvement of the fungal biocontrol agent Trichoderma atroviride to enhance both antagonism and induction of plant systemic disease resistance, AEM 71 (7)(2005) 3959-3965, doi:10.1128/AEM.71.7.3959-3965.2005.

[22] K. Chugh, B.A. Wallace, Peptaibols: models for ion channels, Biochem. Soc. Trans. 29 (4) (2001) 565-570, doi:10.1042/bst0290565.

[23] W. Clarke, A. Dasgupta, Clinical Challenges in Therapeutic Drug Monitoring:Spe- cial Populations, Physiological Conditions and Pharmacogenomics, Elsevier, 2016.

[24] P. Cosette, S. Rebuffat, B. Bodo, G. Molle, The ion-channel activity of longibrachins LGA I and LGB II: effects of Pro-2/Ala and Gln-18/Glu substitutions on the alame- thicin voltage-gated membrane channels, Biochim. Biophys. Acta Biomembr. 1461(1) (1999) 113-122, doi:10.1016/S0005-2736(99)00153-4.

[25] J.F. Daniel, E.Rodrigues Filho, Peptaibols of trichoderma, Nat. Prod. Rep. 24 (5)(2007) 1128-1141, doi:10.1039/B618086H.

[26] P.R. Das, B.N. Pramanik, Fast atom bombardment mass spectrometric characteri- zation of peptides, Mol. Biotechnol. 9 (1998) 141-154, doi:10.1007/BF02760815.

[27] T. Degenkolb, A. Berg, W. Gams, B. Schlegel, U. Gräfe, The occurrence of peptai- bols and structurally related peptaibiotics in fungi and their mass spectrometric identification via diagnostic fragment ions, J. Pept. Sci. 9 (11-12) (2003) 666-678, doi:10.1002/psc.497.

[28] T. Degenkolb, T. Gräfenhan, A. Berg, H.I Nirenberg, W. Gams, H. Brück- ner, Peptaibiomics: screening for polypeptide antibiotics (peptaibiotics) from plant protective Trichoderma species, Chem. Biodivers. 3 (6) (2006) 593-610, doi:10.1002/cbdv.200690063.

[29] T. Degenkolb, H. Brückner, Peptaibiomics: towards a myriad of bioactive pep- tides containing C 𝛼-dialkylamino acids? Chem. Biodivers. 5 (9) (2008) 1817-1843, doi:10.1002/cbdv.200890171.

[30] A.C. Dianoux, A. Tsugita, M. Przybylski, Mass spectral identification of the blocked N- terminal tryptic peptide of the ATPase inhibitor from beef heart mitochondria, FEBS Lett. 174 (1) (1984) 151-156, doi:10.1016/0014-5793(84)81095-9.

[31] B. Domon, R. Aebersold, Mass spectrometry and protein analysis, Science 312 (5771) (2006) 212-217, doi:10.1126/science.1124619.

[32] F.Y. Du, X.M. Li, Z.C. Sun, L.H. Meng, B.G. Wang, Secondary metabolites with agricultural antagonistic potentials from Beauveria felina, a marine-derived en- tomopathogenic fungus, J. Agric. Food Chem. 68 (50) (2020) 14824-14831, doi:10.1021/acs.jafc.0c05696.

[33] D. Duval, S. Rebuffat, C. Goulard, Y. Prigent, M. Becchi, B. Bodo, Isolation and sequence analysis of the peptide antibiotics trichorzins PA from Trichoderma harzianum, J. Chem. Soc. 14 (1997) 2147-2154, doi:10.1039/A700244K.

[34] Y. Elad, I. Chet, Y. Henis, A selective medium for improving quantitative isolation of Trichoderma spp. from soil, Phytoparasitica 9 (1981) 59-67.

[35] J. Engelberth, T. Koch, G. Schüler, N. Bachmann, J. Rechtenbach, W. Boland, Ion channel-forming alamethicin is a potent elicitor of volatile biosynthesis and tendril coiling. Cross talk between jasmonate and salicylate signaling in lima bean, Plant Physiol. 125 (1) (2001) 369-377, doi:10.1104/pp.125.1.369.

[36] K. Fuji, E. Fujita, T.Fujita Y.Takaishi, I. Arita, M. Komatsu, N. Hiratsuka, New an- tibiotics, trichopolyns A and B: isolation and biological activity, Experientia 34 (1978) 237-239, doi:10.1007/BF01944702.

[37] T. Fujita, S.I. Wada, A. Iida, T. Nishimura, M. Kanai, N. Toyama, Fun- gal metabolites. XIII. Isolation and structural elucidation of new peptaibols, trichodecenins-I and-II, from Trichoderma viride, Chem. 42 (3) (1994) 489-494, doi:10.1248/cpb.42.489.

[38] K. Gaudich, M. Przybylski, Field desorption mass spectrometric characterization of thiol conjugates related to the oxidative metabolism of the anticancer drug 4′ -(9-acridinylamino)-methanesulfon-m-anisidide, Biomed. Mass Spectrom. 10 (4)(1983) 292-299, doi:10.1002/bms.1200100412.

[39] G.L. Glish, R.W. Vachet, The basics of mass spectrometry in the twenty-first century, Nat. Rev. Drug Discov. 2 (2) (2003) 140-150, doi:10.1038/nrd1011.

[40] C. Goulard, S. Hlimi, S. Rebuffat, B. Bodo, Trichorzins HA. MA, antibiotic peptides from Trichoderma harzianum. I. Fermentation, isolation and biological properties, J. Antibiot. 48 (11) (1995) 1248-1253, doi:10.7164/antibiotics.48.1248.

[41] M.E. Hajji, S. Rebuffat, D. Lecommandeur, B. Bodo, Isolation and sequence determination of trichorzianines A antifungal peptides from Trichoderma harzianum, Int. J. Pept. Protein Res. 29 (2) (1987) 207-215, doi:10.1111/j.1399-3011.1987.tb02247.x.

[42] D. Hernández-Gordillo, M. del Rocío Ortega-Gómez, L. Galicia-Polo, A. Castorena-Maldonado, A. Vergara-López, M.A. Guillén-González, L. Torre-Bouscoulet, Sleep apnea in patients with acromegaly. Frequency, characterization and positive pres- sure titration, Respir. Med. 6 (2012) 28, doi:10.2174/1874306401206010028.

[43] C.T. Hou, A. Ciegler, C.W. Hesseltine, New mycotoxin A. Trichotoxin, from Tri- choderma viride isolated from southern leaf blight-infected corn, Appl. Microbiol. 23 (1) (1972) 183-185, doi:10.1128/am.23.1.183-185.1972.

[44] X. Hou, R. Sun, Y. Feng, R. Zhang, T. Zhu, Q. Che, G. Zhang, D. Li, Peptai- bols: diversity, bioactivity, and biosynthesis, Eur. J. Biochem. (2022) 100026, doi:10.1016/j.engmic.2022.100026.

[45] Q. Huang, Y. Tezuka, Y. Hatanaka, T. Kikuchi, A. Nishi, K. Tubaki, Studies on metabolites of mycoparasitic fungi. IV. Minor peptaibols of Trichoderma kiningii, Chem. 43 (10) (1995) 1663-1667, doi:10.1248/cpb.43.1663.

[46] G.J. Hughes, K.J. Wilson, High-performance liquid chromatography: analytic and preparative applications in protein-structure determination, Methods Biochem. Anal. (1983) 59-136, doi:10.1002/9780470110492.ch3.

[47] A. Iida, T. Mihara, T. Fujita, Y. Takaishi, Peptidic immunosuppressants from the fungus Trichoderma polysporum, Bioorg. Med. Chem. 9 (24) (1999) 3393-3396, doi:10.1016/S0960-894X(99)00621-6.

[48] G. Irmscher, G. Jung, Die hämolytischen Eigenschaften der membranmodifizieren- den Peptidantibiotika Alamethicin, Suzukacillin und Trichotoxin, Eur. J. Biochem. 80 (1) (1977) 165-174, doi:10.1111/j.1432-1033.1977.tb11868.x.

[49] A. Jaworski, H. Brückner, Detection of new sequences of peptaibol antibi- otics trichotoxins A-40 by on-line liquid chromatography-electrospray ion- ization mass spectrometry, J. Chromatogr. A 862 (2) (1999) 179-189, doi:10.1016/S0021-9673(99)00931-0.

[50] W.H. Jiao, Z. Khalil, P. Dewapriya, A.A. Salim, H.W. Lin, R.J. Capon, Tricho- dermides A-E: new peptaibols isolated from the Australian termite nest-derived fungus Trichoderma virens CMB-TN16, J. Nat. Prod. 81 (4) (2018) 976-984, doi:10.1021/acs.jnatprod.7b01072.

[51] A. Jozala, Fermentation processes, Editor, BoD-Books on Demand, 2017.

[52] Kempka M., Improved mass accuracy in MALDI-TOF-MS analysis (Doctoral disser- tation, KTH), 2005.

[53] W.A. Korfmacher, Foundation review: principles and applications of LC-MS in new drug discovery, Drug Discov. Today 10 (20) (2005) 1357-1367, doi:10.1016/S1359-6446 (05)03620-2.

[54] C. Krause, J. Kirschbaum, H. Brückner, Peptaibiomics: an advanced, rapid and selective analysis of peptaibiotics/peptaibols by SPE/LC-ES-MS, Amino Acids 30 (2006) 435-443, doi:10.1007/s00726-005-0275-9.

[55] K.J. Kumar, V. Vijayan, An overview of liquid chromatography-mass spectroscopy instrumentation, 2014.

[56] A. Landreau, Y.F. Pouchus, C. Sallenave-Namont, J.F. Biard, M.C. Boumard, T.R. du Pont, F. Mondeguer, C. Goulard, J.F. Verbist, Combined use of LC/MS and a biological test for rapid identification of marine mycotoxins produced by Trichoderma koningii, J. Microbiol. Methods 48 (2-3) (2002) 181-194, doi:10.1016/S0167-7012(01)00322-0.

[57] G. Leclerc, S. Rebuffat, C. Goulard, B. Bodo, Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains I. Fermentation and isolation, J. Antibiot. 51 (2) (1998) 170-177, doi:10.7164/antibiotics.51.170.

[58] G. Leclerc, C. Goulard, Y. Prigent, B. Bodo, H. Wróblewski, S. Rebuffat, Sequences and antimycoplasmic properties of longibrachins LGB II and LGB III, two novel 20-residue peptaibols from Trichoderma l Ongibrachiatum, J. Nat. Prod. 64 (2) (2001) 164-170, doi:10.1021/np000240s.

[59] B. Leitgeb, A. Szekeres, L. Manczinger, C. Vágvölgyi, L. Kredics, The history of alamethicin: a review of the most extensively studied peptaibol, Chem. Biodivers. 4 (6) (2007) 1027-1051.

[60] X.Y. Li, Z.C. Mao, Y.H. Wang, Y.X. Wu, Y.Q. He, C.L. Long, ESI LC-MS and MS/MS characterization of antifungal cyclic lipopeptides produced by Bacillus subtilis XF-1, Microb. Physiol. 22 (2) (2012) 83-93, doi:10.1159/000338530.

[61] C.K. Lim, G. Lord, Current developments in LC-MS for pharmaceutical analysis, Biol. Pharm. Bull. 25 (5) (2002) 47-57, doi:10.1248/bpb.25.547.

[62] M. Lorito, V. Farkas, S. Rebuffat, B. Bodo, C.P. Kubicek, Cell wall synthesis is a major target of mycoparasitic antagonism by Trichoderma harzianum, J. Bacteriol. 178 (21) (1996) 6382-6385, doi:10.1128/jb.178.21.6382-6385.1996.

[63] L. Maddau, A. Cabras, A. Franceschini, B.T. Linaldeddu, S. Crobu, T. Roggio, D. Pagnozzi, Occurrence and characterization of peptaibols from Trichoderma citrinoviride, an endophytic fungus of cork oak, using electrospray ionization quadrupole time-of-flight mass spectrometry, Microbiology 155 (10) (2009) 3371-3381, doi:10.1099/mic.0.030916-0.

[64] M. Mann, R.C. Hendrickson, A. Pandey, Analysis of proteins and proteomes by mass spectrometry, Annu. Rev. Biochem. 70 (1) (2001) 437-473, doi:10.1146/an- nurev.biochem.70.1.437.

[65] T. Marik, C. Tyagi, G. Raci ć, D. Rakk, A. Szekeres, C. Vágvölgyi, L. Kredics, New 19- residue peptaibols from Trichoderma clade Viride, Microorganisms 6 (3) (2018) 85, doi:10.3390/microorganisms6030085.

[66] G.R. Marshall, E.E. Hodgkin, D.A. Langs, G.D. Smith, J. Zabrocki, M.T. Lep- lawy, Factors governing helical preference of peptides containing multiple 𝛼, 𝛼-dialkyl amino acids, Proc. Natl. Acad. Sci. U.S.A. 87 (1) (1990) 487-491, doi:10.1073/pnas.87.1.48.

[67] S. Matei, G.M. Matei, P. Cornea, G. Popa, Characterization of soil Trichoderma isolates for potential biocontrol of plant pathogens, Soil Forming Factors Processes Temperate Zone 10 (1) (2011) 29-37.

[68] A.J. Martin, R.L. Synge, A new form of chromatogram employing two liquid phases: a theory of chromatography. 2. Application to the micro-determination of the higher monoamino-acids in proteins, Biochem 35 (12) (1941) 1358, doi:10.1042/bj0351358.

[69] C.E. Meyer, F. Reusser, A polypeptide antibacterial agent isolated from Tricho- derma viride, Experientia 23 (1967) 85-86, doi:10.1007/BF02135929.

[70] C.L. Meyers, Column chromatography, Curr. Protoc. Nucleic Acid Chem. 3 (1)(2000) A-3E.

[71] R. Mikkola, M.A. Andersson, L. Kredics, P.A. Grigoriev, N. Sundell, M.S. Salkinoja-Salonen, 20-Residue and 11-residue peptaibols from the fungus T richoderma lon- gibrachiatum are synergistic in forming N a + /K + -permeable channels and ad- verse action towards mammalian cells, FEBS J. 279 (22) (2012) 4172-4190, doi:10.1111/febs.12010.

[72] M. Mohamed-Benkada, M. Montagu, J.F. Biard, F. Mondeguer, P. Verite, M. Dal- galarrondo, J. Bissett, Y.F. Pouchus, New short peptaibols from a marine Tricho- derma strain. Rapid communications in mass spectrometry: an international journal devoted to the rapid dissemination of up-to-the-minute, Res. Mass Spectrometry 20 (8) (2006) 1176-1180, doi:10.1002/rcm.2430.

[73] V. Monaco, E. Locardi, F. Formaggio, M. Crisma, S. Mammi, E. Peggion, C. To- niolo, S. Rebuffat, B. Bodo, Solution conformational analysis of amphiphilic heli- cal, synthetic analogs of the lipopeptaibol trichogin GAIV, Pept. Res. 52 (4) (1998) 261-272, doi:10.1111/j.1399-3011.1998.tb01240.x.

[74] P.K. Mukherjee, A. Wiest, N. Ruiz, A. Keightley, M.E. Moran-Diez, K. McCluskey, Y.F. Pouchus, C.M. Kenerley, Two classes of new peptaibols are synthesized by a single non-ribosomal peptide synthetase of Trichoderma virens, J. Biol. Chem. 286 (6) (2011) 4544-4554, doi:10.1074/jbc.M110.159723.

[75] T. Neuhof, R. Dieckmann, I.S. Druzhinina, C.P. Kubicek, H. von Döhren, Intact-cell MALDI-TOF mass spectrometry analysis of peptaibol formation by the genus Trichoderma/Hypocrea: can molecular phylogeny of species predict peptaibol structures? Microbiology 153 (10) (2007) 3417-3437, doi:10.1099/mic.0.2007/006692-0.

[76] T. Neuhof, A. Berg, H. Besl, T. Schwecke, R. Dieckmann, H. von Döhren, Peptaibol production by Sepedonium strains parasitizing Boletales, Chem. Biodivers. 4 (6)(2007) 1103-1115, doi:10.1002/cbdv.200790099.

[77] A.P. New, C. Eckers, N.J. Haskins, W.A. Neville, S. Elson, J.A. Hueso-Rodríguez, A. Rivera-Sagredo, Structures of polysporins AD, four new peptaibols isolated from Trichoderma polysporum, Tetrahedron Lett. 37 (1) (1996) 3039-3042, doi:10.1016/0040-4039(96)00463-7.

[78] S.U. Oh, S.J.Lee B.S.Yun, J.H. Kim, I.D. Yoo, Atroviridins AC and neoatroviridins AD, novel peptaibol antibiotics produced by Trichoderma atroviride F80317 I. tax- onomy, fermentation, isolation and biological activities, J. Antibiot. 55 (6) (2002) 557-564, doi:10.7164/antibiotics.55.557.

[79] S.U. Oh, B.S. Yun, S.J. Lee, I.D. Yoo, Structures and biological activities of novel antibiotic peptaibols neoatroviridins AD from Trichoderma atroviride F80317, J. Microbiol. Biotechnol. 15 (2) (2005) 384-387.

[80] S. Pan, L. Liu, W. Wang, Identification of antibiotic peptaibols from fermentation broth of Trichoderma harzianum, Chin. J. Biol. 28 (4) (2012) 528.

[81] Y Pecci, F Rivardo, MG Martinotti, G. Allegrone, LC/ESI-MS/MS character- isation of lipopeptide biosurfactants produced by the Bacillus licheniformis V9T14 strain, J. Mass Spectrom. 45 (7) (2010) 772-778, doi:10.1002/jms. 1767.

[82] J.J. Pitt, Principles and applications of liquid chromatography-mass spectrometry in clinical biochemistry, Clin. Biochem. Rev. 30 (1) (2009) 19.

[83] M. Przybylski, Fast atom bombardment and field desorption mass spectrometry, Fresnius’ Z, Anal. Chem. 315 (5) (1983).

[84] P.R. Tamandegani, D. Zafari, T. Marik, A. Szekeres, C. Vágvölgyi, L. Kredics, in: Current trends in synthesis, identification and drug delivery, 2nd Iranian Peptide Conf. and humboldt kolleg: bioactive molecules: current trends in synthesis, iden- tification and drug delivery: Book of abstracts, Iranian Peptide Society, Iran, 2017, p. 26.

[85] P.R. Tamandegani, T. Marik, D. Zafari, D. Balázs, C. Vágvölgyi, A. Szekeres, L. Kredics, Changes in peptaibol production of Trichoderma species during in vitro antagonistic interactions with fungal plant pathogens, Biomolecules 10 (5) (2020) 730, doi:10.3390/biom10050730.

[86] M.S. Rawa, T. Nogawa, A. Okano, Y. Futamura, H.A. Wahab, H. Osada, Zealpep- taibolin, an 11-mer cytotoxic peptaibol group with 3 Aib-Pro motifs isolated from Trichoderma sp. RK10-F026, J. antibiotics. 74 (8) (2021) 485-495.

[87] H. Razafindralambo, M. Paquot, C. Hbid, P. Jacques, J. Destain, P. Thonart, Purification of antifungal lipopeptides by reversed-phase high- performance liquid chromatography, J. Chromatogr. A 639 (1) (1993) 81-85, doi:10.1016/0021-9673(93)83091-6.

[88] S. Rebuffat, M.O. El hajji, P. Hennig, D. Davoust, B. Bodo, Isolation, sequence, and conformation of seven trichorzianines from Trichoderma harzianum, Int. J. Pept. 34 (3) (1989) 200-210, doi:10.1111/j.1399-3011.1989.tb00231.x.

[89] S. Rebuffat, C. Goulard, B. Bodo, Antibiotic peptides from Trichoderma harzianum: harzianins HC, proline-rich 14-residue peptaibols, J. Chem. Soc. 14 (1995) 1849-1855, doi:10.1039/P19950001849.

[90] J. Ren, C. Xue, L. Tian, M. Xu, J. Chen, Z. Deng, P. Proksch, W. Lin, Asperelines A- F, peptaibols from the marine-derived fungus Trichoderma asperellum, J. Nat. Prod. 72 (6) (2009) 1036-1044, doi:10.1021/np900190w.

[91] J.L. Reino, R.F. Guerrero, R. Hernandez-Galan, I.G. Collado, Secondary metabolites from species of the biocontrol agent Trichoderma, Phytochem. Rev. 7 (2008) 89-123, doi:10.1007/s11101-006-9032-2.

[92] K.L. Rinehart Jr., L.A. Gaudioso M.L. Moore R.C. Pandey Jr., JC. Cook M. Bar- ber R.D. Sedgwick R.S. Bordoli A.N. Tyler B.N. Green, Structures of eleven zervamicin and two emerimicin peptide antibiotics studied by fast atom bom- bardment mass spectrometry, J. Am. Chem. Soc. 103 (21) (1981) 6517-6520, doi:10.1021/ja00411a052.

[93] A. Ritieni, V. Fogliano, D. Nanno, G. Randazzo, C. Altomare, G. Perrone, A. Bottalico, L. Maddau, F. Marras, Paracelsin E, a new peptaibol from Tricho- derma saturnisporum, J. Nat. Prod. 58 (11) (1995) 1745-1748, doi:10.1021/ np50125a017.

[94] J. Rivera-Chávez, H.A. Raja, T.N. Graf, J.M. Gallaghe, P. Metri, D. Xue, C.J. Pearce, N.H. Oberlies, Prealamethicin F50 and related peptaibols from Trichoderma arun- dinaceum: validation of their authenticity via in situ chemical analysis, RSC Adv. 7 (72) (2017) 45733-45741, doi:10.1039/C7RA09602J.

[95] C.R. Röhrich, A. Vilcinskas, H. Brückner, T. Degenkolb, The sequences of the eleven-residue peptaibiotics: Suzukacillins-B, Chem. Biodivers. 10 (5) (2013) 827-837, doi:10.1002/cbdv.201200384.

[96] N. Ruiz, G. Wielgosz-Collin, L. Poirier, O. Grovel, K.E. Petit, M. Mohamed-Benkada, T.R. du Pont, J. Bissett, P. Vérité, G. Barnathan, Y.F. Pouchus, New Trichobrachins, 11- residue peptaibols from a marine strain of Trichoderma longibrachiatum, Pep- tides 28 (7) (2007) 1351-1358, doi:10.1016/j.peptides.2007.05.012.

[97] C. Sallenave, Y.F. Pouchus, M. Bardouil, P. Lassus, M.F. Roquebert, J.F. Verbist, Bioaccumulation of mycotoxins by shellfish: contamination of mussels by metabo- lites of a Trichoderma koningii strain isolated in the marine environment, Toxicon 37 (1) (1999) 77-83, doi:10.1016/S0041-0101(98)00135-4.

[98] M. Santiago, S. Strobel, in: Thin Layer chromatography, InMethods in En- zymology, 533, Academic Press, 2013, pp. 303-324, doi:10.1016/B978-0-12-420067-8.00024-6.

[99] S.K. Satpute, A.G. Banpurkar, P.K. Dhakephalkar, I.M. Banat, B.A. Chopade, Meth- ods for investigating biosurfactants and bioemulsifiers: a review, Crit. Rev. Biotech- nol. 30 (2) (2010) 127-144, doi:10.3109/07388550903427280.

[100] J. Schiller, R. Suß, J. Arnhold, B. Fuchs, J. Leßig, M. Muller, M. Petkovie, H. Spal- teholz, O. Zschornig, K. Arnold, Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry in lipid and phospholipid research, Prog. Lipid Res. 43 (2004) 449, doi:10.1016/j.plipres.2004.08.001.

[101] R. Schuhmacher, N. Stoppacher, S. Zeilinger, Peptaibols of Trichoderma atroviride: screening, identification, and structure elucidation by liquid chromatography-tan- dem mass spectrometry, Commun. Curr. Res. Educat. Topics Trends Appl. Micro- biol. 108 (2007) 609-616.

[102] J. Sherma, B. Fried, Handbook of Thin-Layer Chromatography, 3rd edition, Marcel Dekker, Inc. New York, 2003.

[103] W.L. Shi, X.L. Chen, L.X. Wang, Z.T. Gong, S. Li, C.L. Li, B.B. Xie, W. Zhang, M. Shi, C. Li, Y.Z. Zhang, Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibi- otics mainly produced by Trichoderma spp, J. Exp. Bot. 67 (8) (2016) 2191-2205, doi:10.1093/jxb/erw023.

[104] L. Signor, E.B. Erba, Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometric analysis of intact proteins larger than 100 kDa, J. Vis. Exp. 79 (2013) e50635, doi:10.3791/50635.

[105] A. Singh, M. Shahid, M. Srivastava, S. Pandey, A. Sharma, V. Kumar, Optimal physical parameters for growth of Trichoderma species at varying pH, temper- ature and agitation, Virol. Mycol. 3 (1) (2014) 1-7, doi:10.4172/2161-0517. 1000127.

[106] V.P. Singh, N. Yedukondalu, V. Sharma, M. Kushwaha, R. Sharma, A. Chaubey, A. Kumar, D. Singh, R.A. Vishwakarma, Lipovelutibols A-D: cytotoxic lipopeptai- bols from the Himalayan cold habitat fungus Trichoderma velutinum, J. Nat. Prod. 81 (2) (2018) 219-226, doi:10.1021/acs.jnatprod.6b00873.

[107] V.P. Singh, A.S. Pathania, M. Kushwaha, S. Singh, V. Sharma, F.A. Malik, I.K. Khan, A. Kumar, D. Singh, R.A. Vishwakarma, 14-Residue peptaibol velutibol A from Trichoderma velutinum: its structural and cytotoxic evaluation, RSC Adv. 10 (52)(2020) 31233-31242, doi:10.1039/D0RA05780K.

[108] V.P. Singh, A.S. Pathania, S. Sharma, F.A. Malik, A. Kumar, D. Singh, R.A. Vish- wakarma, Total synthesis and conformational analysis of naturally occurring lipovelutibols along with lead optimization of lipovelutibol D, ACS Omega 6 (9)(2021) 6070-6080, doi:10.1021/acsomega.0c04038.

[109] A. Sinha, D. Harshita, R. Singh, S.G. Rao, A. Verma, Comprehensive evaluation of Trichoderma harzianum and Trichoderma viride on different culture media & at different temperature and pH, Pharma Innov. J. 7 (2018) 193-195.

[110] X.Y. Song, S.T. Xie, X.L. Chen, C.Y. Sun, M. Shi, Y.Z. Zhang, Solid-state fermenta- tion for Trichokonins production from Trichoderma koningii SMF2 and preparative purification of Trichokonin VI by a simple protocol, J. Biotechnol. 131 (2) (2007) 209-215, doi:10.1016/j.jbiotec.2007.06.012.

[111] X. Song, Y. Zhang, Y. Wang, Antimicrobial peptides peptaibols from trichoderma-a review, Acta Microbiol. Sin. 514 (4) (2011) 438-444.

[112] N. Stoppacher, B. Reithner, M. Omann, S. Zeilinger, R. Krska, R. Schuhmacher, Profiling of trichorzianines in culture samples of Trichoderma atroviride by liquid chromatography/tandem mass spectrometry, Rapid Commun. Mass Spectrom. 21 (24) (2007) 3963-3970 RCM, doi:10.1002/rcm.3301.

[113] A. Szekeres, B. Leitgeb, L. Kredics, Z. Antal, L. Hatvani, L. Manczinger, C. Vágvöl- gyi, Peptaibols and related peptaibiotics of Trichoderma, Acta Microbiol. Immunol. Hung. 52 (2) (2005) 137-168, doi:10.1556/amicr.52.2005.2.2.(119).

[114] M. Tabachnik, “Method for Growing Trickoderma, ”U.S. 4,837,155, Taylor, 1989.

[115] P. Tempst, L.E. Hood, S.B. Kent, Practical high performance liquid chromatography of proteins and peptides, High Performance Liquid Chromatogr. Plant Sci. (1987) 170-208.

[116] C. Toniolo, M. Crisma, F. Formaggio, C. Peggion, R.F. Epand, R.M. Lipopeptaibols, A novel family of membrane active, antimicrobial peptides, Cell. Mol. Life Sci. 58 (2001) 1179-1188.

[117] I. Touati, N. Ruiz, O. Thomas, I.S. Druzhinina, L. Atanasova, O. Tabbene, S. Elka- houi, R. Benzekri, L. Bouslama, Y.F. Pouchus, F. Limam, Hyporientalin A, an an- ti-Candida peptaibol from a marine Trichoderma orientale, World J. Microbiol. Biotechnol. 34 (2018) 1-2.

[118] M.J. Torres, C.P. Brandan, G. Petroselli, R. Erra-Balsells, M.C. Audisio, Antago- nistic effects of Bacillus subtilis subsp. subtilis and B. amyloliquefaciens against Macrophomina phaseolina: SEM study of fungal changes and UV-MALDI-TOF MS analysis of their bioactive compounds, Microbiol. Res. 182 (2016) 31-39, doi:10.1016/j.micres.2015.09.005.

[119] P. Urajová, J. Hájek, M. Wahlsten, J. Jokela, T. Galica, D.P. Fewer, A. Kust, E. Zapom ělová-Kozlíková, K. Delawská, K. Sivonen, J. Kopecký, A liquid chromatography-mass spectrometric method for the detection of cyclic 𝛽-amino fatty acid lipopeptides, J. Chromatogr. A 1438 (2016) 76-83, doi:10.1016/j.chroma.2016.02.013.

[120] A.I. Van Bohemen, N. Ruiz, A. Zalouk-Vergnoux, A. Michaud, T. Robiou du Pont, I. Druzhinina, L. Atanasova, S. Prado, B. Bodo, L. Meslet-Cladiere, B. Cochereau, Pentadecaibins I-V: 15-residue peptaibols produced by a marine-derived Tricho- derma sp. of the Harzianum clade, J. Nat. Prod. 84 (4) (2021) 1271-1282, doi:10.1021/acs.jnatprod.0c01355.

[121] J. Víglaš S. Dobiasová J. Viktorová T. Ruml V. Repiská P. Olejníková H. Gbel- cová Peptaibol-containing extracts of trichoderma atroviride and the fight against resistant microorganisms and cancer cells, Molecules 26 (19) (2021) 6025, doi:10.3390/molecules26196025.

[122] C. Wang, D. Xiao, B. Dun, A.S.Tsega M.Yin, L. Xie, W. Li, Q. Yue, S. Wang, H. Gao, M. Lin, Chemometrics and genome mining reveal an unprecedented family of sugar acid-containing fungal nonribosomal cyclodepsipeptides, Proc. Natl. Acad. Sci. U. S. A. 119 (32) (2022), doi:10.1073/pnas.2123379119.

[123] L. Whitmore, B. Wallace, Peptaibols, in: Handbook of Biologically Active Peptides, Academic Press, 2006, pp. 83-88.

[124] A. Wiest, D. Grzegorski, B.W. Xu, C. Goulard, S. Rebuffat, D.J. Ebbole, B. Bodo, C. Kenerley, Identification of peptaibols from Trichoderma virens and cloning of a peptaibol synthetase, J. Biol. Chem. 277 (23) (2002) 20862-20868, doi:10.1074/jbc.M201654200.

[125] D. Xiao, M. Zhang, P. Wu, T. Li, W. Li, L. Zhang, Q. Yue, X. Chen, X. Wei, Y. Xu, C. Wang, Halovirs I-K, antibacterial and cytotoxic lipopeptaibols from the plant pathogenic fungus Paramyrothecium roridum NRRL 2183, J. Antibiot. 75 (5)(2022) 247-257, doi:10.1038/s41429-022-00517-7.

[126] S. Yamamoto, S. Shiraishi, S. Suzuki, Are cyclic lipopeptides produced by Bacillus amyloliquefaciens S13-3 responsible for the plant defence response in strawberry against Colletotrichum gloeosporioides? Lett. Appl. Microbiol. 60 (4) (2015) 379-386, doi:10.1111/lam.12382.

[127] H. Yang, X. Li, X. Li, H. Yu, Z. Shen, Identification of lipopeptide iso- forms by MALDI-TOF-MS/MS based on the simultaneous purification of iturin, fengycin, and surfactin by RP-HPLC, Anal. Bioanal. Chem. 407 (2015) 2529-2542, doi:10.1007/s00216-015-8486-8.

[128] B.S. Yun, Y.H.Kim I.D.Yoo, Y.S. Kim, S.J. Lee, K.S. Kim, W.H. Yeo, Peptaivirins A and B, two new antiviral peptaibols against TMV infection, Tetrahedron Lett. 41 (9) (2000) 1429-1431, doi:10.1016/S0040-4039(99)02308-4.

[129] S.H. Zhang, X.Zhao X.L.Yue, J. Tang, Y. Yang, R. Xu, H. Ma, S.M. Zhu, F.Y. Luo, Q. Zhang, G.G. Zhang, Longibrachiamide A, a 20-residue peptaibol isolated from trichoderma longibrachiatum Rifai DMG-3-1-1, Chem. Biodivers 19 (6) (2022), doi:10.1002/cbdv.202200286.