{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T12:18:21Z","timestamp":1777378701809,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010485","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000}}],"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Nature Science Foundation of China","doi-asserted-by":"crossref","award":["81873960,81601746"],"award-info":[{"award-number":["81873960,81601746"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Dematiaceous <jats:italic>Fonsecaea monophora<\/jats:italic> is one of the major pathogens of chromoblastomycosis. It has been well established that melanization is catalyzed by the type I polyketide synthase (PKS) in <jats:italic>F<\/jats:italic>. <jats:italic>monophora<\/jats:italic>. Multidomain protein Type I PKS is encoded by six genes, in which the last enzyme thioesterase (TE) catalyzes the cyclization and releases polyketide. Two PKS genes AYO21_03016 (<jats:italic>pks1<\/jats:italic>) and AYO21_10638 have been found in <jats:italic>F<\/jats:italic>. <jats:italic>monophora<\/jats:italic> and both PKS loci have the same gene arrangement but the TE domain in AYO21_10638 is truncated at 3\u2019- end. TE may be the key enzyme to maintain the function of <jats:italic>pks1<\/jats:italic>. To test this hypothesis, we constructed a 3\u2019-end 500 bp deletion mutant of AYO21_03016 (<jats:italic>\u0394pks1-TE-C500<\/jats:italic>) and its complemented strain. We profiled metabolome of this mutant and analyzed the consequences of impaired metabolism in this mutant by fungal growth <jats:italic>in vitro<\/jats:italic> and by pathogenesis <jats:italic>in vivo<\/jats:italic>. Compared with wild-type strain, we found that the mutant repressed <jats:italic>pks1<\/jats:italic> expression and other 5 genes expression levels were reduced by more than 50%, perhaps leading to a corresponding melanin loss. The mutant also reduced sporulation and delayed germination, became vulnerable to various environmental stresses and was less resistance to macrophage or neutrophil killings <jats:italic>in vitro<\/jats:italic>, and less virulence in mice footpad model. Metabolomic analysis indicated that many metabolites were remarkably affected in <jats:italic>\u0394pks1-TE-C500<\/jats:italic>, in particular, an increased nicotinamide and antioxidant glutathione. In conclusion, we confirmed the crucial role of C-terminal TE in maintaining fully function of <jats:italic>pks1<\/jats:italic> in <jats:italic>F<\/jats:italic>. <jats:italic>monophora<\/jats:italic>. Deletion of TE negatively impacts on the synthesis of melanin and metabolites that eventually affect growth and virulence of <jats:italic>F<\/jats:italic>. <jats:italic>monophora<\/jats:italic>. Any potential inhibitor of TE then could be a novel antifungal target for drug development.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010485","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T17:50:16Z","timestamp":1655142616000},"page":"e0010485","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8389-0544","authenticated-orcid":true,"given":"Minying","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiying","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiufeng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4352-2533","authenticated-orcid":true,"given":"Hongfang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1504-0147","authenticated-orcid":true,"given":"Liyan","family":"Xi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"pntd.0010485.ref001","unstructured":"WHO. 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