{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T23:43:42Z","timestamp":1783813422281,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["41706077"],"award-info":[{"award-number":["41706077"]}]},{"name":"National Natural Science Foundation of China","award":["81903494"],"award-info":[{"award-number":["81903494"]}]},{"name":"National Natural Science Foundation of China","award":["2019M652309"],"award-info":[{"award-number":["2019M652309"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["41706077"],"award-info":[{"award-number":["41706077"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["81903494"],"award-info":[{"award-number":["81903494"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M652309"],"award-info":[{"award-number":["2019M652309"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The biocontrol fungus Trichoderma harzianum, from both marine and terrestrial environments, has attracted considerable attention. T. harzianum has a tremendous potential to produce a variety of bioactive secondary metabolites (SMs), which are an important source of new herbicides and antibiotics. This review prioritizes the SMs of T. harzianum from 1988 to June 2022, and their relevant biological activities. Marine-derived SMs, especially terpenoids, polyketides, and macrolides compounds, occupy a significant proportion of natural products from T. harzianum, deserving more of our attention.<\/jats:p>","DOI":"10.3390\/md20110701","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T02:11:15Z","timestamp":1668046275000},"page":"701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Structures and Biological Activities of Secondary Metabolites from Trichoderma harzianum"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3587-5969","authenticated-orcid":false,"given":"Rui","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0621-2779","authenticated-orcid":false,"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hand and Foot Surgery, Affiliated Hospital of Qingdao University, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4611-8955","authenticated-orcid":false,"given":"Xiaoping","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1039\/D0NP00089B","article-title":"Marine natural products","volume":"38","author":"Carroll","year":"2021","journal-title":"Nat. Prod. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"566691","DOI":"10.3389\/fmicb.2020.566691","article-title":"Iron uptake mechanisms in marine phytoplankton","volume":"11","author":"Sutak","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1021\/acs.jnatprod.8b00345","article-title":"Spiro-phthalides and isocoumarins isolated from the marinesponge-derived fungus Setosphaeria sp. SCSIO41009","volume":"81","author":"Pang","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1039\/D1NP00076D","article-title":"Marine natural products","volume":"39","author":"Carroll","year":"2022","journal-title":"Nat. Prod. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.1002\/cbic.201700462","article-title":"Harzianone biosynthesis by the biocontrol fungus Trichoderma","volume":"18","author":"Barra","year":"2017","journal-title":"ChemBioChem"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5598\/imafungus.2015.06.02.02","article-title":"Accepted Trichoderma names in the year 2015","volume":"6","author":"Bissett","year":"2015","journal-title":"IMA Fungus"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Khan, R.A.A., Najeeb, S., Hussain, S., Xie, B., and Li, Y. (2020). Bioactive secondary metabolites from Trichoderma spp. against phytopathogenic fungi. Microorganisms, 8.","DOI":"10.3390\/microorganisms8060817"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1080\/14786419.2018.1486311","article-title":"An endophytic fungus from Trichoderma harzianum SWUKD3.1610 that produces nigranoic acid and its analogues","volume":"33","author":"Han","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1080\/14786419.2018.1522314","article-title":"Two new sesquiterpenoids from the marine-sediment-derived fungus Trichoderma harzianum P1\u20134","volume":"33","author":"Fang","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"ref_10","first-page":"123","article-title":"Harzianic acid: A novel siderophore from Trichoderma harzianum","volume":"347","author":"Vinale","year":"2013","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.tetlet.2013.11.107","article-title":"Tandyukisin, a novel ketoaldehyde decalin derivative, produced by a marine sponge-derived Trichoderma harzianum","volume":"55","author":"Yamada","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27596","DOI":"10.1039\/C8RA04865G","article-title":"Harzianumnones A and B: Two hydroxyanthraquinones from the coral-derived fungus Trichoderma harzianum","volume":"8","author":"Shi","year":"2018","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13345","DOI":"10.1038\/s41598-019-49778-7","article-title":"Potent phytotoxic harziane diterpenes from a soft coral-derived strain of the fungus Trichoderma harzianum XS-20090075","volume":"9","author":"Zhao","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3389\/fmicb.2020.00572","article-title":"Terpenoids from the coral-derived fungus Trichoderma harzianum (XS-20090075) induced by chemical epigenetic manipulation","volume":"11","author":"Shi","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yamada, T., Suzue, M., Arai, T., Kikuchi, T., and Tanaka, R. (2017). Trichodermanins C-E, new diterpenes with a fused 6-5-6-6 ring system produced by a marine sponge-derived fungus. Mar. Drugs, 15.","DOI":"10.3390\/md15060169"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yamada, T., Fujii, A., and Kikuchi, T. (2019). New diterpenes with a fused 6-5-6-6 ring system isolated from the marine sponge-derived fungus Trichoderma harzianum. Mar. Drugs, 17.","DOI":"10.3390\/md17080480"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1021\/acs.jnatprod.8b00714","article-title":"Diterpenes and sesquiterpenes from the marine algicolous Fungus Trichoderma harzianum X-5","volume":"81","author":"Song","year":"2018","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.bmc.2018.12.038","article-title":"Harzianoic acids A and B, new natural scaffolds with inhibitory effects against hepatitis C virus","volume":"27","author":"Li","year":"2019","journal-title":"Bioorg. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1002\/jlac.199719971224","article-title":"15-Hydroxyacorenone: New acorane-type sesquiterpene from the culture broth of the mycoparasitic fungus Trichoderma harzianum","volume":"12","author":"Tezuka","year":"1997","journal-title":"Liebigs Ann. Recl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1080\/10286020.2020.1729752","article-title":"Naphthalene derivatives and halogenate quinoline from the coral-derived fungus Trichoderma harzianum (XS-20090075) through OSMAC approach","volume":"23","author":"Yu","year":"2021","journal-title":"J. Asian. Nat. Prod. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1080\/14786419.2014.958739","article-title":"Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity","volume":"29","author":"Ahluwalia","year":"2015","journal-title":"Nat. Prod. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1080\/14786419.2019.1574782","article-title":"Trichosordarin A, a norditerpene glycoside from the marine-derived fungus Trichoderma harzianum R5","volume":"34","author":"Liang","year":"2020","journal-title":"Nat. Prod. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1080\/10286020.2015.1042371","article-title":"New C13 lipids from the marine-derived fungus Trichoderma harzianum","volume":"17","author":"Li","year":"2015","journal-title":"J. Asian. Nat. Prod. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5070","DOI":"10.1016\/j.tetlet.2016.10.004","article-title":"Tandyukisins E and F, novel cytotoxic decalin derivatives isolated from a marine sponge-derived fungus","volume":"57","author":"Suzue","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.3390\/md13053231","article-title":"Determination of the chemical structures of tandyukisins B-D, isolated from a marine sponge-derived fungus","volume":"13","author":"Yamada","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1021\/np50105a019","article-title":"Isolation and structure of harzianum A: A new trichothecene from Trichoderma harzianum","volume":"57","author":"Corley","year":"1994","journal-title":"J. Nat. Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"990","DOI":"10.7164\/antibiotics.49.990","article-title":"Harziphilone and fleephilone, two new HIV REV\/RRE binding inhibitors produced by Trichoderma harzianum","volume":"49","author":"Huang","year":"1996","journal-title":"J. Antibiot."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1021\/np50100a020","article-title":"Antifungal metabolites from Trichoderma harzianum","volume":"56","author":"Ghisalberti","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7925","DOI":"10.1016\/S0040-4039(00)61513-7","article-title":"Trichoharzin, a new polyketide produced by the imperfect fungus Trichoderma harzianum separated from the marine sponge Micale cecilia","volume":"34","author":"Kobayashi","year":"1993","journal-title":"Tetrahedron Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1472-765X.2006.01939.x","article-title":"Major secondary metabolites produced by two commercial Trichoderma strains active against different phytopathogens","volume":"43","author":"Vinale","year":"2006","journal-title":"Lett. Appl. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1021\/acs.jafc.5b01258","article-title":"Trichoharzianol, a new antifungal from Trichoderma harzianum F031","volume":"63","author":"Jeerapong","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.7164\/antibiotics.51.33","article-title":"Cytotoxic substances produced by a fungal strain from a sponge: Physico-chemical properties and structures","volume":"51","author":"Amagata","year":"1998","journal-title":"J. Antibiot."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12324","DOI":"10.1021\/jacs.6b07588","article-title":"Homodimericin A: A complex hexacyclic fungal metabolite","volume":"138","author":"Mevers","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","first-page":"1078","article-title":"Chemical interaction among termite-associated microbes","volume":"43","author":"Mevers","year":"2017","journal-title":"Chem. Eng. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1021\/jm00397a002","article-title":"Novel type of potential anticancer agents derived from chrysophanol and emodin. Some structure-activity relationship studies","volume":"31","author":"Koyama","year":"1988","journal-title":"J. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1074\/jbc.M209367200","article-title":"Inhibition of protein kinase CK2 by anthraquinone-related compounds","volume":"278","author":"Moro","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jbbm.2006.09.003","article-title":"Efficient isolation of anthraquinone-derivatives from Trichoderma harzianum ETS 323","volume":"70","author":"Liu","year":"2007","journal-title":"J. Biochem. Biophys. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7288","DOI":"10.1021\/jf901405c","article-title":"Study on the anthraquinones separated from the cultivation of Trichoderma harzianum strain Th-R16 and their biological activity","volume":"57","author":"Liu","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100026","DOI":"10.1016\/j.engmic.2022.100026","article-title":"Peptaibols: Diversity, bioactivity, and biosynthesis","volume":"2","author":"Hou","year":"2022","journal-title":"Eng. Microbiol."},{"key":"ref_40","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. Pharma. Bull."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1139\/v96-020","article-title":"Peptaibol metabolites of Tolypocladium geodes","volume":"74","author":"Tsantrizos","year":"1996","journal-title":"Can. J. Chem."},{"key":"ref_42","first-page":"1587","article-title":"Harzianin HB I, an 11-residue peptaibol from Trichoderma harzianum: Isolation, sequence, solution synthesis and membrane activity","volume":"1","author":"Rebuffat","year":"1997","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.7164\/antibiotics.48.1254","article-title":"Trichorzins HA and MA, antibiotic peptides from Trichoderma harzianum II. Sequence determination","volume":"48","author":"Hlimi","year":"1995","journal-title":"J. Antibiot."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1248\/cpb.43.392","article-title":"Fungal metabolities. XVIII. New membrane-modifying peptides, trichorozins I-IV, from the fungus trichoderma harzianum","volume":"43","author":"Iida","year":"1995","journal-title":"Chem. Pharm. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1039\/p19950001849","article-title":"Antibiotic peptides from Trichoderma harzianum: Harzianins HC, proline-rich 14-residue peptaibols","volume":"1","author":"Rebuffat","year":"1995","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"170","DOI":"10.7164\/antibiotics.51.170","article-title":"Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains I. Fermentation and isolation","volume":"51","author":"Leclerc","year":"1998","journal-title":"J. Antibiot."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0005-2736(89)90504-X","article-title":"Interaction of trichorzianines A and B with model membranes and with the amoeba Dictyostelium","volume":"978","author":"Hajji","year":"1989","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1399-3011.1989.tb00231.x","article-title":"Isolation, sequence, and conformation of seven trichorzianines B from Trichoderma harzianum","volume":"34","author":"Rebuffat","year":"1989","journal-title":"Int. J. Pept. Protein Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.3389\/fmicb.2020.01495","article-title":"Antifungal nafuredin and epithiodiketopiperazine derivatives from the mangrove-derived fungus Trichoderma harzianum D13","volume":"11","author":"Zhao","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"731","DOI":"10.7164\/antibiotics.47.731","article-title":"Harzianic acid, a new antimicrobial antibiotic from a fungus","volume":"47","author":"Sawa","year":"1994","journal-title":"J. Antibiot."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"9760","DOI":"10.3390\/molecules19079760","article-title":"A novel fungal metabolite with beneficial properties for agricultural applications","volume":"19","author":"Vinale","year":"2014","journal-title":"Molecules"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1021\/np50124a022","article-title":"Koshino, H. MR-93A, a new oxazole from Trichoderma harzianum KCTC 0114BP","volume":"58","author":"Lee","year":"1995","journal-title":"J. Nat. Prod."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"474","DOI":"10.7164\/antibiotics.50.474","article-title":"MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma harzianum II. Physico-chemical properties and structural elucidation","volume":"50","author":"Lee","year":"1997","journal-title":"J. Antibiot."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"469","DOI":"10.7164\/antibiotics.50.469","article-title":"MR566A and MR566B, new melanin synthesis inhibitors produced by Trichoderma harzianum I. Taxonomy, fermentation, isolation and biological Activities","volume":"50","author":"Lee","year":"1997","journal-title":"J. Antibiot."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1016\/S0040-4039(01)00355-0","article-title":"Absolute configuration of nafuredin, a new specific NADH-fumarate reductase inhibitor","volume":"42","author":"Takano","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1021\/np990066b","article-title":"Dichlorodiaportin, diaportinol, and diaportinic acid: Three novel isocoumarins from Penicillium nalgiovense","volume":"62","author":"Larsen","year":"1999","journal-title":"J. Nat. Prod."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/nph.13725","article-title":"The volatile 6-pentyl-2H-pyran-2-one from Trichoderma atroviride regulates Arabidopsis thaliana root morphogenesis via auxin signaling and ETHYLENE INSENSITIVE 2 functioning","volume":"209","year":"2016","journal-title":"New Phytol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/701\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:13:27Z","timestamp":1760145207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/11\/701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["md20110701"],"URL":"https:\/\/doi.org\/10.3390\/md20110701","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]}}}