{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T15:44:01Z","timestamp":1792251841134,"version":"4.4.0"},"reference-count":91,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2024-536"],"award-info":[{"award-number":["075-15-2024-536"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peptaibols are linear fungal peptides featuring \u03b1,\u03b1-dialkylated amino acids (e.g., \u03b1-aminoisobutyric acid (Aib), isovaline (Iva)) and characteristic C-terminal alcohol groups. Despite their promising antibacterial and antiplasmodial activities, detailed biosynthetic studies remain limited. A genome-guided study of the fungus Trichodema sp. SK1-7, isolated from decaying wood, revealed the production of previously described trichorozin IV (1), along with novel SF4-type peptaibol 2 (trichorozin V). The structures of these compounds were elucidated through MS analysis, NMR study and advanced Marfey\u2019s method. The genome of Trichoderma sp. SK1-7 harbors two PKS-NRPS hybrid gene clusters containing 14 and 18 adenylation domains. Analysis of the modular architecture suggested that trichorozins are synthesized by a 14-module protein via a module skipping mechanism. Genome mining revealed several types of short peptaibol synthase architectures (10\u201314 adenylation domains) across various Trichoderma species, accompanied by similar long peptaibol synthases. Furthermore, putative Aib\/Iva biosynthesis machinery in Trichoderma was identified, showing specific architectures potentially involved in regulating peptaibol biosynthesis. Feeding experiments demonstrated that peptaibol production depends on the ratio of Iva\/Aib. The isolated compounds exhibited moderate antibacterial and cytotoxic activities along with a synergistic effect when combined with membrane-targeting antibiotics. Our findings suggest that genome-guided approaches hold promise for further development of peptabiotics with a wide range of applications, including antibiotic adjuvants.<\/jats:p>","DOI":"10.3390\/ijms26125599","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T11:18:40Z","timestamp":1749640720000},"page":"5599","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genome-Guided Metabolomic Profiling of Peptaibol-Producing Trichoderma"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0922-2203","authenticated-orcid":false,"given":"Arseniy A.","family":"Sinichich","sequence":"first","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Department of Chemistry, Lomonosov Moscow State University, Kolmogorova 1, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-5873","authenticated-orcid":false,"given":"Danil V.","family":"Krivonos","sequence":"additional","affiliation":[{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"},{"name":"Research Institute for Systems Biology and Medicine (RISBM), 18 Nauchniy Proezd, 117246 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Baranova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8527-3540","authenticated-orcid":false,"given":"Mikhail Y.","family":"Zhitlov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Department of Chemistry, Lomonosov Moscow State University, Kolmogorova 1, 119992 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5603-5371","authenticated-orcid":false,"given":"Olga A.","family":"Belozerova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav A.","family":"Lushpa","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Moscow Center for Advanced Studies, Kulakova Str. 20, 123592 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Vvedensky","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), 18 Nauchniy Proezd, 117246 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-8215","authenticated-orcid":false,"given":"Marina V.","family":"Serebryakova","sequence":"additional","affiliation":[{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskie Gory, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia I.","family":"Kalganova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8620-6998","authenticated-orcid":false,"given":"Arsen M.","family":"Kudzhaev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-5506","authenticated-orcid":false,"given":"Yuri A.","family":"Prokopenko","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4636-1840","authenticated-orcid":false,"given":"Sofia S.","family":"Sinelnikova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0807-1864","authenticated-orcid":false,"given":"Ekaterina A.","family":"Trusova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey I.","family":"Kovalchuk","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0130-5079","authenticated-orcid":false,"given":"Elena N.","family":"Ilina","sequence":"additional","affiliation":[{"name":"Research Institute for Systems Biology and Medicine (RISBM), 18 Nauchniy Proezd, 117246 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0452","authenticated-orcid":false,"given":"Stanislav S.","family":"Terekhov","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-5890","authenticated-orcid":false,"given":"Vera A.","family":"Alferova","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 1-40 Leninskie Gory, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hou, X., Sun, R., Feng, Y., Zhang, R., Zhu, T., Che, Q., Zhang, G., and Li, D. (2022). Peptaibols: Diversity, Bioactivity, and Biosynthesis. Eng. Microbiol., 2.","DOI":"10.1016\/j.engmic.2022.100026"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pereira-Dias, L., Oliveira-Pinto, P.R., Fernandes, J.O., Regalado, L., Mendes, R., Teixeira, C., Mariz-Ponte, N., Gomes, P., and Santos, C. (2023). Peptaibiotics: Harnessing the Potential of Microbial Secondary Metabolites for Mitigation of Plant Pathogens. Biotechnol. Adv., 68.","DOI":"10.1016\/j.biotechadv.2023.108223"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1016\/j.apsb.2025.02.036","article-title":"Marine-Derived New Peptaibols with Antibacterial Activities by Targeting Bacterial Membrane Phospholipids","volume":"15","author":"Chen","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1021\/acs.jafc.4c08847","article-title":"Genome Mining Reveals Biosynthesis of the Antifungal Lipopeptaibols, Texenomycins, through a Hybrid PKS-NRPS System, in the Fungus Marian","volume":"73","author":"Jiao","year":"2025","journal-title":"Elegans. J. Agric. Food Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1994","DOI":"10.1021\/acs.jnatprod.4c00438","article-title":"Cytotoxic Peptaibols from Trichoderma Guizhouense, a Fungus Isolated from an Urban Soil Sample","volume":"87","author":"Han","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20763","DOI":"10.1021\/acs.jafc.4c01952","article-title":"Synergistic Effect of Two Peptaibols from Biocontrol Fungus Trichoderma Longibrachiatum Strain 40418 on CO-Induced Plant Resistance","volume":"72","author":"Luo","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.1021\/acs.jafc.4c00493","article-title":"New Antibacterial Peptaibiotics against Plant and Fish Pathogens from the Deep-Sea-Derived Fungus Simplicillium Obclavatum EIODSF 020","volume":"72","author":"Liang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6315","DOI":"10.1021\/acs.jafc.3c08984","article-title":"Isolation, Characterization, and Bioherbicidal Potential of the 16-Residue Peptaibols from Emericellopsis Sp. XJ1056","volume":"72","author":"Song","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.chembiol.2023.10.025","article-title":"Antiplasmodial Peptaibols Act through Membrane Directed Mechanisms","volume":"31","author":"Collins","year":"2024","journal-title":"Cell Chem. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1021\/acs.jnatprod.0c01370","article-title":"Leveraging Peptaibol Biosynthetic Promiscuity for Next-Generation Antiplasmodial Therapeutics","volume":"84","author":"Lee","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bmcl.2004.02.074","article-title":"A Novel 11-Residual Peptaibol-Derived Carrier Peptide for in Vitro Oligodeoxynucleotide Delivery into Cell","volume":"14","author":"Wada","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1002\/cbdv.200790090","article-title":"A Functionalized 20-Residue Peptaibol Derivative for Nucleic Acid Delivery","volume":"4","author":"Wada","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1016\/j.bmc.2012.03.054","article-title":"Cellular Uptake of Covalent Conjugates of Oligonucleotide with Membrane-Modifying Peptide, Peptaibol","volume":"20","author":"Wada","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6776","DOI":"10.1016\/j.bmc.2014.10.040","article-title":"Aib-Containing Peptide Analogs: Cellular Uptake and Utilization in Oligonucleotide Delivery","volume":"22","author":"Wada","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"E8957","DOI":"10.1073\/pnas.1707565114","article-title":"Unique Amalgamation of Primary and Secondary Structural Elements Transform Peptaibols into Potent Bioactive Cell-Penetrating Peptides","volume":"114","author":"Du","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/bst0290565","article-title":"Peptaibols: Models for Ion Channels","volume":"29","author":"Chugh","year":"2001","journal-title":"Biochem. Soc. Trans."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D699","DOI":"10.1093\/nar\/gkt1183","article-title":"MycoCosm Portal: Gearing up for 1000 Fungal Genomes","volume":"42","author":"Grigoriev","year":"2014","journal-title":"Nucl. Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1021\/acs.jnatprod.0c01186","article-title":"Emerimicins V\u2013X, 15-Residue Peptaibols Discovered from an Acremonium Sp. through Integrated Genomic and Chemical Approaches","volume":"84","author":"Wu","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nakatani, T., Koga, A., Goto, S., Inoue, M., Shigedomi, K., Seki, K., Araki, K., Taira, J., Kodama, H., and Osada, S. (2024). Importance of Isoleucine Residue in Ion Channel Formation Ability of 11-Residue Peptaibols. Bioorg. Med. Chem., 110.","DOI":"10.1016\/j.bmc.2024.117839"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dalla Torre, C., Sannio, F., Battistella, M., Docquier, J.-D., and De Zotti, M. (2023). Peptaibol Analogs Show Potent Antibacterial Activity against Multidrug Resistant Opportunistic Pathogens. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097997"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1074\/jbc.M110.159723","article-title":"Two Classes of New Peptaibols Are Synthesized by a Single Non-Ribosomal Peptide Synthetase of Trichoderma Virens","volume":"286","author":"Mukherjee","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1002\/psc.498","article-title":"Isolation, Structure Elucidation and Biological Activities of Trichofumins A, B, C and D, New 11 and 13mer Peptaibols from Trichoderma Sp. HKI 0276","volume":"9","author":"Berg","year":"2003","journal-title":"J. Pept. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/cbdv.201100212","article-title":"The Production of Multiple Small Peptaibol Families by Single 14-Module Peptide Synthetases in Trichoderma\/Hypocrea","volume":"9","author":"Degenkolb","year":"2012","journal-title":"Chem. Biodivers."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3417","DOI":"10.1099\/mic.0.2007\/006692-0","article-title":"Intact-Cell MALDI-TOF Mass Spectrometry Analysis of Peptaibol Formation by the Genus Trichoderma\/Hypocrea: Can Molecular Phylogeny of Species Predict Peptaibol Structures?","volume":"153","author":"Neuhof","year":"2007","journal-title":"Microbiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/cbdv.201400300","article-title":"Peptaibol, Secondary-Metabolite, and Hydrophobin Pattern of Commercial Biocontrol Agents Formulated with Species of the Trichoderma Harzianum Complex","volume":"12","author":"Degenkolb","year":"2015","journal-title":"Chem. Biodivers."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1248\/cpb.42.1070","article-title":"Fungal Metabolites. XVI. Structures of New Peptaibols, Trichokindins I-VII, from the Fungus Trichoderma Harzianum","volume":"42","author":"Iida","year":"1994","journal-title":"Chem. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1021\/acs.jnatprod.2c00153","article-title":"Tolypocladamide H and the Proposed Tolypocladamide NRPS in Tolypocladium Species","volume":"85","author":"Tehan","year":"2022","journal-title":"J. Nat. Prod."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fan, J., Ren, J., He, R., Wei, P.-L., Li, Y., Li, W., Chen, D., Druzhinina, I.S., Li, Z., and Yin, W.-B. (2022). Biosynthetic Diversification of Peptaibol Mediates Fungus-Mycohost Interactions. bioRxiv.","DOI":"10.1101\/2022.06.05.494846"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Castro, G.S., Sousa, T.F., Da Silva, G.F., Pedroso, R.C.N., Menezes, K.S., Soares, M.A., Dias, G.M., Santos, A.O., Yamagishi, M.E.B., and Faria, J.V. (2023). Characterization of Peptaibols Produced by a Marine Strain of the Fungus Trichoderma Endophyticum via Mass Spectrometry, Genome Mining and Phylogeny-Based Prediction. Metabolites, 13.","DOI":"10.3390\/metabo13020221"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1093\/bioinformatics\/btab007","article-title":"Clinker & Clustermap.Js: Automatic Generation of Gene Cluster Comparison Figures","volume":"37","author":"Gilchrist","year":"2021","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Terlouw, B.R., Huang, C., Meijer, D., Cediel-Becerra, J.D.D., Rothe, M.L., Jenner, M., Zhou, S., Zhang, Y., Fage, C.D., and Tsunematsu, Y. (2025). PARAS: High-Accuracy Machine-Learning of Substrate Specificities in Nonribosomal Peptide Synthetases. bioRxiv.","DOI":"10.1101\/2025.01.08.631717"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/cbic.200400282","article-title":"Structure and Biosynthesis of Myxochromides S1\u20133 in Stigmatella Aurantiaca : Evidence for an Iterative Bacterial Type I Polyketide Synthase and for Module Skipping in Nonribosomal Peptide Biosynthesis","volume":"6","author":"Wenzel","year":"2005","journal-title":"ChemBioChem"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.1128\/AAC.00007-06","article-title":"Biosynthetic Gene Cluster for the Polyenoyltetramic Acid \u03b1-Lipomycin","volume":"50","author":"Bihlmaier","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1128\/AEM.03160-15","article-title":"The Siderophore Metabolome of Azotobacter Vinelandii","volume":"82","author":"Baars","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Masschelein, J., Mattheus, W., Gao, L.-J., Moons, P., Van Houdt, R., Uytterhoeven, B., Lamberigts, C., Lescrinier, E., Rozenski, J., and Herdewijn, P. (2013). A PKS\/NRPS\/FAS Hybrid Gene Cluster from Serratia Plymuthica RVH1 Encoding the Biosynthesis of Three Broad Spectrum, Zeamine-Related Antibiotics. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054143"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1002\/jlac.199719970421","article-title":"Structures of Peptaibol Antibiotics Hypomurocin A and B from the Ascomycetous Fungus Hypocrea Muroiana Hino et Katsumoto","volume":"1997","author":"Becker","year":"1997","journal-title":"Liebigs Ann."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/psc.621","article-title":"Fungal Biosynthesis of Non-Ribosomal Peptide Antibiotics and \u03b1, \u03b1-Dialkylated Amino Acid Constituents","volume":"11","author":"Raap","year":"2005","journal-title":"J. Pept. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/cbdv.200800331","article-title":"Aib and Iva in the Biosphere: Neither Rare nor Necessarily Extraterrestrial","volume":"6","author":"Becker","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"15827","DOI":"10.1002\/anie.202104644","article-title":"Aziridine Formation by a FeII \/\u03b1-Ketoglutarate Dependent Oxygenase and 2-Aminoisobutyrate Biosynthesis in Fungi","volume":"60","author":"Bunno","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1021\/acs.orglett.3c04185","article-title":"Characterization of Aziridine-Forming \u03b1-Ketoglutarate-Dependent Oxygenase in L-Isovaline Biosynthesis","volume":"26","author":"Zhou","year":"2024","journal-title":"Org. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6240","DOI":"10.1021\/jacs.2c12664","article-title":"Mechanistic Studies of Aziridine Formation Catalyzed by Mononuclear Non-Heme Iron Enzymes","volume":"145","author":"Cha","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate Structure Prediction of Biomolecular Interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/s00249-003-0348-1","article-title":"Analysis of Peptaibol Sequence Composition: Implications for in Vivo Synthesis and Channel Formation","volume":"33","author":"Whitmore","year":"2004","journal-title":"Eur. Biophys. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1021\/acs.jnatprod.4c00590","article-title":"Cytotoxic Peptaibols from Trichoderma Strigosum","volume":"87","author":"Park","year":"2024","journal-title":"J. Nat. Prod."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1039\/D4NP00009A","article-title":"Advances, Opportunities, and Challenges in Methods for Interrogating the Structure Activity Relationships of Natural Products","volume":"41","author":"Ancajas","year":"2024","journal-title":"Nat. Prod. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7510","DOI":"10.1039\/C8SC02046A","article-title":"Synthetic Biology Approaches and Combinatorial Biosynthesis towards Heterologous Lipopeptide Production","volume":"9","author":"Yan","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12934-018-0929-4","article-title":"Module and Individual Domain Deletions of NRPS to Produce Plipastatin Derivatives in Bacillus Subtilis","volume":"17","author":"Gao","year":"2018","journal-title":"Microb. Cell Fact."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/s41429-021-00429-y","article-title":"Zealpeptaibolin, an 11-Mer Cytotoxic Peptaibol Group with 3 Aib-Pro Motifs Isolated from Trichoderma Sp. RK10-F026","volume":"74","author":"Rawa","year":"2021","journal-title":"J. Antibiot."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4172","DOI":"10.1111\/febs.12010","article-title":"20-Residue and 11-residue Peptaibols from the Fungus T Richoderma Longibrachiatum Are Synergistic in Forming Na+\/K+-permeable Channels and Adverse Action towards Mammalian Cells","volume":"279","author":"Mikkola","year":"2012","journal-title":"FEBS J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ijpddr.2018.03.005","article-title":"Synergistic Combination of Alkylphosphocholines with Peptaibols in Targeting Leishmania Infantum in Vitro","volume":"8","author":"Fragiadaki","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Setargie, A., Wang, C., Zhang, L., and Xu, Y. (2024). Chromatographic and Mass Spectroscopic Guided Discovery of Trichoderma Peptaibiotics and Their Bioactivity. Eng. Microbiol., 4.","DOI":"10.1016\/j.engmic.2023.100135"},{"key":"ref_52","unstructured":"Keller, R. (2004). The Computer Aided Resonance Assignment Tutorial, Cantina."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"W\u00fcthrich, K. (1986). NMR of Proteins and Nucleic Acids, Wiley-Interscience.","DOI":"10.1051\/epn\/19861701011"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s00726-004-0118-0","article-title":"Marfey\u2019s Reagent for Chiral Amino Acid Analysis: A Review","volume":"27","author":"Bhushan","year":"2004","journal-title":"Amino Acids"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1055\/s-0031-1289727","article-title":"A Convenient One-Step Synthesis of Stable \u03b2-Amino Alcohol N-Boranes from \u03b1-Amino Acids","volume":"44","author":"Pinaka","year":"2012","journal-title":"Synthesis"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Kim, C.-K., Krumpe, L.R.H., Smith, E., Henrich, C.J., Brownell, I., Wendt, K.L., Cichewicz, R.H., O\u2019Keefe, B.R., and Gustafson, K.R. (2021). Roseabol A, a New Peptaibol from the Fungus Clonostachys Rosea. Molecules, 26.","DOI":"10.3390\/molecules26123594"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1021\/acs.jnatprod.5b01125","article-title":"C3 and 2D C3 Marfey\u2019s Methods for Amino Acid Analysis in Natural Products","volume":"79","author":"Vijayasarathy","year":"2016","journal-title":"J. Nat. Prod."},{"key":"ref_58","unstructured":"Nanoporetech (2025, March 21). GitHub\u2014Nanoporetech\/Dorado: Oxford Nanopore\u2019s Basecaller. GitHub., Available online: https:\/\/Github.Com\/Nanoporetech\/Dorado."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/s41587-019-0072-8","article-title":"Assembly of Long, Error-Prone Reads Using Repeat Graphs","volume":"37","author":"Kolmogorov","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Walker, B.J., Abeel, T., Shea, T., Priest, M., Abouelliel, A., Sakthikumar, S., Cuomo, C.A., Zeng, Q., Wortman, J., and Young, S.K. (2014). Pilon: An Integrated Tool for Comprehensive Microbial Variant Detection and Genome Assembly Improvement. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112963"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/bioinformatics\/btr010","article-title":"A Novel Hybrid Gene Prediction Method Employing Protein Multiple Sequence Alignments","volume":"27","author":"Keller","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"W46","DOI":"10.1093\/nar\/gkad344","article-title":"antiSMASH 7.0: New and Improved Predictions for Detection, Regulation, Chemical Structures and Visualisation","volume":"51","author":"Blin","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Slater, G.S.C., and Birney, E. (2005). Automated Generation of Heuristics for Biological Sequence Comparison. BMC Bioinform., 6.","DOI":"10.1186\/1471-2105-6-31"},{"key":"ref_64","unstructured":"Innis, M.A., Gelfand, D.H., Sninsky, J.J., and White, T.J. (1990). 38\u2014Amplification and Direct Sequencing of Fungal Ribosomal RNA Genes for Phylogenetics. PCR Protocols: A Guide to Methods and Applications, Academic Press."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1080\/00275514.1999.12061051","article-title":"A Method for Designing Primer Sets for Speciation Studies in Filamentous Ascomycetes","volume":"91","author":"Carbone","year":"1999","journal-title":"Mycologia"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/oxfordjournals.molbev.a026092","article-title":"Phylogenetic Relationships among Ascomycetes: Evidence from an RNA Polymerse II Subunit","volume":"16","author":"Liu","year":"1999","journal-title":"Mol. Biol. Evol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e01532-20","DOI":"10.1128\/AEM.01532-20","article-title":"MIST: A Multilocus Identification System for Trichoderma","volume":"86","author":"Dou","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkf436","article-title":"MAFFT: A Novel Method for Rapid Multiple Sequence Alignment Based on Fast Fourier Transform","volume":"30","author":"Katoh","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Price, M.N., Dehal, P.S., and Arkin, A.P. (2010). FastTree 2\u2014Approximately Maximum-Likelihood Trees for Large Alignments. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009490"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"W52","DOI":"10.1093\/nar\/gkz333","article-title":"OrthoVenn2: A Web Server for Whole-Genome Comparison and Annotation of Orthologous Clusters across Multiple Species","volume":"47","author":"Xu","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/molbev\/msy096","article-title":"MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms","volume":"35","author":"Kumar","year":"2018","journal-title":"Mol. Biol. Evolut."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1021\/acs.biochem.9b00735","article-title":"The EFI Web Resource for Genomic Enzymology Tools: Leveraging Protein, Genome, and Metagenome Databases to Discover Novel Enzymes and Metabolic Pathways","volume":"58","author":"Zallot","year":"2019","journal-title":"Biochemistry"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Oberg, N., Zallot, R., and Gerlt, J.A. (2023). EFI-EST, EFI-GNT, and EFI-CGFP: Enzyme Function Initiative (EFI) Web Resource for Genomic Enzymology Tools. J. Mol. Biol., 435.","DOI":"10.1016\/j.jmb.2023.168018"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Kubicek, C.P., Herrera-Estrella, A., Seidl-Seiboth, V., Martinez, D.A., Druzhinina, I.S., Thon, M., Zeilinger, S., Casas-Flores, S., Horwitz, B.A., and Mukherjee, P.K. (2011). Comparative Genome Sequence Analysis Underscores Mycoparasitism as the Ancestral Life Style of Trichoderma. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-4-r40"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Proctor, R.H., McCormick, S.P., Kim, H.-S., Cardoza, R.E., Stanley, A.M., Lindo, L., Kelly, A., Brown, D.W., Lee, T., and Vaughan, M.M. (2018). Evolution of Structural Diversity of Trichothecenes, a Family of Toxins Produced by Plant Pathogenic and Entomopathogenic Fungi. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006946"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Druzhinina, I.S., Chenthamara, K., Zhang, J., Atanasova, L., Yang, D., Miao, Y., Rahimi, M.J., Grujic, M., Cai, F., and Pourmehdi, S. (2018). Massive Lateral Transfer of Genes Encoding Plant Cell Wall-Degrading Enzymes to the Mycoparasitic Fungus Trichoderma from Its Plant-Associated Hosts. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007322"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1099\/mic.0.030916-0","article-title":"Occurrence and Characterization of Peptaibols from Trichoderma Citrinoviride, an Endophytic Fungus of Cork Oak, Using Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry","volume":"155","author":"Maddau","year":"2009","journal-title":"Microbiology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e01747-15","DOI":"10.1128\/genomeA.01747-15","article-title":"Draft Whole-Genome Sequence of Trichoderma Gamsii T6085, a Promising Biocontrol Agent of Fusarium Head Blight on Wheat","volume":"4","author":"Baroncelli","year":"2016","journal-title":"Genome Announc."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Marik, T., Tyagi, C., Raci\u0107, G., Rakk, D., Szekeres, A., V\u00e1gv\u00f6lgyi, C., and Kredics, L. (2018). New 19-Residue Peptaibols from Trichoderma Clade Viride. Microorganisms, 6.","DOI":"10.3390\/microorganisms6030085"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Niu, X., Thaochan, N., and Hu, Q. (2020). Diversity of Linear Non-Ribosomal Peptide in Biocontrol Fungi. J. Fungi, 6.","DOI":"10.3390\/jof6020061"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"4996","DOI":"10.1128\/AEM.70.8.4996-5004.2004","article-title":"Biological Effects of Trichoderma Harzianum Peptaibols on Mammalian Cells","volume":"70","author":"Peltola","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1039\/a700244k","article-title":"Isolation and Sequence Analysis of the Peptide Antibiotics Trichorzins PA from Trichoderma Harzianum","volume":"1","author":"Duval","year":"1997","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.7164\/antibiotics.48.1248","article-title":"Trichorzins HA and MA, Antibiotic Peptides from Trichoderma Harzianum. I. Fermentation, Isolation and Biological Properties","volume":"48","author":"Goulard","year":"1995","journal-title":"J. Antibiot."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1248\/cpb.43.1663","article-title":"Studies on Metabolites of Mycoparasitic Fungi. IV. Minor Peptaibols of Trichoderma Koningii","volume":"43","author":"Huang","year":"1995","journal-title":"Chem. Pharm. Bull."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Rahimi Tamandegani, P., Marik, T., Zafari, D., Bal\u00e1zs, D., V\u00e1gv\u00f6lgyi, C., Szekeres, A., and Kredics, L. (2020). Changes in Peptaibol Production of Trichoderma Species during In Vitro Antagonistic Interactions with Fungal Plant Pathogens. Biomolecules, 10.","DOI":"10.3390\/biom10050730"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1021\/np000240s","article-title":"Sequences and Antimycoplasmic Properties of Longibrachins LGB II and LGB III, Two Novel 20-Residue Peptaibols from Trichoderma l Ongibrachiatum","volume":"64","author":"Leclerc","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1002\/cbdv.201500159","article-title":"Identification and Biological Activities of Long-Chain Peptaibols Produced by a Marine-Derived Strain of Trichoderma Longibrachiatum","volume":"13","author":"Pagniez","year":"2016","journal-title":"Chem. Biodivers."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nbt1403","article-title":"Genome Sequencing and Analysis of the Biomass-Degrading Fungus Trichoderma Reesei (Syn. Hypocrea Jecorina)","volume":"26","author":"Martinez","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Li, W.-C., Huang, C.-H., Chen, C.-L., Chuang, Y.-C., Tung, S.-Y., and Wang, T.-F. (2017). Trichoderma Reesei Complete Genome Sequence, Repeat-Induced Point Mutation, and Partitioning of CAZyme Gene Clusters. Biotechnol. Biofuels, 10.","DOI":"10.1186\/s13068-017-0825-x"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1002\/(SICI)1097-0231(199705)11:8<922::AID-RCM927>3.0.CO;2-N","article-title":"Microheterogeneity Characterization of a Paracelsin Mixture fromTrichoderma Reesei Using High-Energy Collision-Induced Dissociation Tandem Mass Spectrometry","volume":"11","author":"Ritieni","year":"1997","journal-title":"Rapid Commun. Mass Spectrom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5599\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:50:18Z","timestamp":1760032218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":91,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125599"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125599","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]}}}