{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:40:04Z","timestamp":1790422804341,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Queensland and the Institute of Molecular Bioscience"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS\/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation amplified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300).<\/jats:p>","DOI":"10.3390\/molecules27103172","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T21:36:06Z","timestamp":1652736966000},"page":"3172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4636-3133","authenticated-orcid":false,"given":"Amila","family":"Agampodi Dewa","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9285-1720","authenticated-orcid":false,"given":"Zeinab G.","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8483-0455","authenticated-orcid":false,"given":"Ahmed H.","family":"Elbanna","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8341-7754","authenticated-orcid":false,"given":"Robert J.","family":"Capon","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elbanna, A.H., Khalil, Z.G., Bernhardt, P.V., and Capon, R.J. 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