AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derivedPenicillium purpurogenumG59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1–7) and two known (8–9) lipopeptides were isolated together with five known polyketides10–14from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A–G (1–7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1′-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay,1–14inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of1–14in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.Keywords:marine-derived fungus;lipopeptide;penicimutalide;Marfey analysis;polyketide;Penicillium purpurogenum;DES mutagenesis
Shi-Ming Fang,Cheng-Bin Cui,Chang-Wei Li,Chang-Jing Wu,Zhi-Jun Zhang,Li Li,Xiao-Jun Huang,Wen-Cai Ye
Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derivedPenicillium purpurogenumG59. Structures and absolute configurations of1and2were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for1–3were also proposed and discussed. Compounds1and2significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound3also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce1–3, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for1–3production.Keywords:purpurogemutantin;purpurogemutantidin;sesquiterpene;meroterpenoid;structure determination;antitumor activity;Penicillium purpurogenum;marine-derived fungus;DES mutagenesis
Ming-Wen Xia,Cheng-Bin Cui,Chang-Wei Li,Chang-Jing Wu,Ji-Xing Peng,De-Hai Li
Three new and rare chromones, named epiremisporine B (2), epiremisporine B1 (3) and isoconiochaetone C (4), along with three known remisporine B (1), coniochaetone A (5) and methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (6) were isolated from a mutant from the diethyl sulfate (DES) mutagenesis of a marine-derivedPenicillium purpurogenumG59. The structures of2–4including the absolute configurations were determined by spectroscopic methods, especially by NMR analysis and electronic circular dichroism (ECD) experiments in conjunction with calculations. The absolute configuration of the known remisporine B (1) was determined for the first time. Compounds2and3have a rare feature that has only been reported in one example so far. The compounds1–6were evaluated for their cytotoxicity against several human cancer cell lines. The present work explored the great potential of our previous DES mutagenesis strategy for activating silent fungal pathways, which has accelerated the discovery of new bioactive compounds.Keywords:chromone derivatives;remisporine;epiremisporine;isoconiochaetone;ECD;marine-derived fungus;Penicillium purpurogenumG59;DES mutagenesis
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