Control of citrus blue and green molds by Actinomycin X2 and its possible antifungal mechanism.

Citrus blue and green molds caused by Penicillium digitatum, P. italicum, and P. polonicum, are the major postharvest diseases of citrus fruit. In the present study, Actinomycin X2 (Act-X2), a naturally occurring antibiotic produced by Streptomyces species, was found to show excellent antifungal effect against these three pathogens with a minimum inhibitory concentration (MIC) value of 62.5 µg/mL for them all, which was better than the positive control thiophanate-methyl. Act-X2 significantly reduced the percentage of spore germination, and highly inhibited the mycelial growth of P. italicum, P. digitatum, and P. polonicum with EC50 values being 34.34, 13.76, and 37.48 µg/mL, respectively. In addition, Act-X2 greatly decreased the intracellular protein content while increasing the reactive oxygen species (ROS) level and superoxide anion (O2-) content in the mycelia of pathogens. In vivo test indicated that Act-X2 strongly inhibited the infection of navel oranges by these three Penicillium species, with an inhibition percentage of >50% for them all at the concentration of 10 MIC. Transcriptome analysis suggested that Act-X2 might highly influence the ribosomal functions of P. polonicum, which was supported as well by the molecular docking analysis of Act-X2 with some key functional proteins and RNAs of the ribosome. Furthermore, Act-X2 significantly reduced the decay percentage and improved the firmness, color, and sugar-acid ratio of navel oranges spray-inoculated with P. polonicum during the postharvest storage at 4 °C for 60 d.

Green synthesis and biological evaluation of glaucanic acid and dihydrocompactin acid by endophytic fungus Penicillium polonicum from Zingiber officinale.

Fungal endophytes are valued for biosynthesizing chemically diverse metabolic cascade with interesting biological activities. In the current investigation, two compounds were isolated from Penicillium polonicum, an endophyte of Zingiber officinale. The active moieties, glaucanic acid (1) and dihydrocompactin acid (2) were isolated from the ethyl acetate extract of P. polonicum and characterized by NMR and mass spectroscopy. Further, bioactive potential of the isolated compounds was evaluated by antimicrobial, antioxidant and cytotoxicity assays. Compounds 1 and 2 displayed antifungal activity against phytopathogen Colletotrichum gloeosporioides with more than 50% reduction in its growth. Both the compounds exhibited antioxidant activity against free radicals (DPPH and ABTS) and cytotoxicity activity against cancer cell lines respectively. The compounds, glaucanic acid and dihydrocompactin acid are being reported for the first time from an endophytic fungus. This is the first report on the biological activities of Dihydrocompactin acid produced by endophytic fungal strain.

New natural pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß) and iNOS inhibitors identified from Penicillium polonicum through in vitro and in vivo studies.

Overexpression of pro-inflammatory cytokines and iNOS have been found to be concomitant with several chronic inflammatory diseases and hence targeting their inhibition would be a useful therapy for inflammation. In view of this, study on discovery of natural pro-inflammatory cytokines inhibitory lead molecules from Penicillium polonicum, an endophytic fungus isolated from the fresh fruits of Piper nigrum was performed. When the culture broth extract of P. polonicum (EEPP) was subjected to LPS-induced cytokines expression (ELISA in RAW 264.7 cells), it exhibited inhibition of TNF-α, IL-6 and IL-1ß and this encouraged us to do chemical investigation on EEPP to explore the bioactive components. Four compounds isolated and characterised as 3,5-di-tert-butyl-4-hydroxy-phenyl propionic acid (1), 2,4-di-tert-butyl phenol (2), indole 3-carboxylic acid (3) and tyrosol (4) were tested for their effect on the production of TNF-α, IL-1ß and IL-6 in RAW 264.7 cells (ELISA). All the compounds exhibited a highly significant (P < 0.0001) inhibition effect, particularly against IL-1ß (IC50: 4-0.91 µM, 1-2.81 µM, 3-4.38 µM, and 2-5.54 µM). Tyrosol (4) was most active with IC50 values of 0.91, 2.67 and 4.60 µM against IL-1ß, IL-6 and TNF-α, respectively. On observing the potential activity of the compounds, two compositions C1 and C2 were prepared by mixing equimolar concentrations of compounds 1, 2, 3 & 4 (C1) and compounds 1, 2, 3, 4 & piperine (C2) in equal ratio. A synergistic effect was observed with C1 exhibiting potential suppression of IL-6 secretion (IC50 1.91 µM) and C2 against IL-1ß (IC50 5.98 µM). Also, the individual compounds and C1 were effective in controlling iNOS expressions in RAW 264.7 cells (RTPCR). Further, the in vivo performance of the compounds and compositions were studied under two in vivo inflammatory models (LPS-induced endotoxaemia and carrageenan-induced paw oedema). Compounds 1, 2, 3, 4, C1 and C2 at 50 mg/kg oral dose showed a significant control over the LPS-stimulated TNF-α, IL-1ß and IL-6 levels in plasma. C1, C2 and 1 exhibited > 50% pan-cytokine inhibition effect. Under the carrageenan-induced anti-inflammatory model, a significant reduction in the paw oedema measured in terms of the difference in the paw thickness was observed. Further, attenuation of pro-inflammatory cytokines levels following ELISA and RT-PCR experiments in the paw tissue homogenate was in agreement with paw thickness results. All compounds and C1 decreased the iNOS gene expression levels, and also the MPO activity and NO production in the paw tissue homogenate with tyrosol (4) as the most active molecule. Further, the mechanism of action was explored by testing the effect of the compounds on the expression of inflammatory markers using western blot analysis (in vitro). They were found to regulate the expression of pro-form and matured-form of IL-1ß by inhibiting NFκB. Also, the compounds reduced the translocation of the NF-κB subunit p65 to the nucleus. Thus, compounds 3,5-di-tert-butyl-4-hydroxy-phenyl propionic acid (1), 2,4-di-tert-butyl phenol (2), indole 3-carboxylic acid (3) and tyrosol (4) are reported as new natural multiple pro-inflammatory cytokines inhibitory leads. The interesting results of C1 might lay a footing for the development of a new anti-inflammatory composition.

A New Lignan (Polonilignan) and Inhibitors of Nitric Oxide Production from Penicillium polonicum, an Endophytic Fungi of Piper nigrum.

Inhibiting nitric oxide (NO) or its production is found to be of therapeutic benefit. To discover natural small molecule inhibitors of NO production, a bioassay- and LC/MS-guided chemical investigation was done on the metabolites of endophytic fungus isolated from fresh Piper nigrum fruits. The isolated pure strain was identified as Penicillium polonicum by 16S rDNA sequence comparison. The culture broth extract of P. polonicum (EEPP) exhibited a significant reduction of NO production (Griess method) in LPS-stimulated RAW 264.7 cells (P<0.0001). To understand the chemical constituents of bioactive EEPP, column chromatography and p-TLC studies were carried out, which yielded eight pure compounds. They were characterised as botryosphaeridione (1), 3-(3,5-di-tert-butyl-4-hydroxy)phenylpropionic acid (2), variabilone (3), 2,4-di-tert-butylphenol (4), indole-3-carboxylic acid (5), tyrosol (6), ethyl ferulate (7) and a new lignan (8) based on the spectral analysis. The structure elucidation of the new lignan, named polonilignan (8), was based on HR-MS, 1 H- & 13 C-NMR, H-H COSY, HSQC and HMBC spectra. Compounds 2, 4, 5 and 6 showed a significant decrease (P<0.0001) in the production of NO in LPS-induced RAW 264.7 cells. Tyrosol (6) and indole-3-carboxylic acid (5) controlled nitrite release with IC50 values of 22.84 and 55.01 µM, respectively. This is the first report of (i) P. polonicum as an endophytic fungus of pepper fruits, (ii) isolation of compounds 1-8 except 6 from P. polonicum culture broth extract and (iii) NO inhibition effect of 2, 4, 5 and 6.

Five new verrucosidin derivatives from Penicillium polonicum, a deep-sea cold-seep sediment isolated fungus.

Five new verrucosidin derivatives, poloncosidins G-K (1-5), were isolated from the deep sea cold-seep sediment-derived fungus Penicillium polonicum CS-252. Their planar structures were elucidated by discreet analysis of the NMR spectroscopic and HRESIMS spectrometric data. The absolute configurations of compounds 1-5 were deduced from the combination of the modified Mosher's method and quantum chemical calculations of their ECD and NMR (with DP4+ probability analysis) data. The antimicrobial activities against several human- and aquatic-pathogenic bacteria of all the isolated compounds were evaluated and the structure-bioactivity relationship was briefly discussed.

Proteomics study on immobilization of Pb(II) by Penicillium polonicum.

Lead (Pb) is widely distributed in nature and has important industrial applications, while being highly toxic. In this study, the Pb(II) biosorption and immobilization behavior of Penicillium polonicum was investigated through surface morphology observation and multiple experimental analysis. In addition, the molecular mechanism of Pb(II) immobilization was further explored through proteomics. The analysis of the removal ability of P. polonicum to Pb(II) has found that P. polonicum could remove Pb(II) up to 95% (initial 4 mM Pb(II)) in 12 d. Scanning Electron Microscope (SEM) revealed a large amount of Pb(II) adsorbed on the cell wall. Raman and Energy Disperse Spectroscopy (EDS) revealed the formation of large amounts of PbC2O4 minerals extracellularly. Field Emission High-resolution Transmission Electron Microscopy (FE-TEM) found that [Pb5(PO4)3Cl] formed on the cell surface and inside the cells. The iTRAQ technique was used to analyze the characteristics of the changes of proteins during the action between Pb(II) and P. polonicum, which further revealed the mechanism of P. polonicum against Pb(II) and biomineralization. It was found that differential proteins in terms of redox, ion binding, metabolic process and ribosome synthesis were predominant in the GO analysis. Together with some of the characterization experiments above, the mechanisms mentioned above was well explained. The up-regulated expression of related proteins involved in respiratory metabolic pathways, antioxidant stress, and degradation of intracellular hazardous substances in the P. polonicum intracellularly such as succinate dehydrogenase, ATPase and cytochrome c oxidase, could explain the high tolerance of P. polonicum to Pb(II). The up regulation of OAH was responsible for extracellular PbC2O4 production. The up regulation of proteins such as TXN and GFA promoted Pb-glutathione (Pb-GSH) complex formation. This study explores the mechanism of Pb removal by fungi from the proteomic level, and provides new ideas and ways for Pb biogeochemical research.

Verrucosidin Derivatives from the Deep Sea Cold-Seep-Derived Fungus Penicillium polonicum CS-252.

Six novel verrucosidin derivatives, namely, poloncosidins A-F (1-6), together with one known analogue (7), were isolated and identified from the deep-sea-derived fungus Penicillium polonicum CS-252, which was obtained from cold-seep sediments collected in the South China Sea at a depth of 1183 m. Their structures were mainly established on the basis of a detailed interpretation of NMR spectroscopic and mass spectrometric data. The relative and absolute configurations of compounds 1-6 were determined by ECD calculations and a DP4+ probability analysis. Compounds 1-5 represent the first examples of verrucosidins with a 2,5-dihydrofuran ring which is uncommon among the known analogues. These compounds exhibited inhibitory activities against several human and aquatic pathogens with MIC values ranging from 4 to 32 µg/mL.

Renal Apoptosis in the Mycotoxicology of Penicillium polonicum and Ochratoxin A in Rats.

Penicillium polonicum K. M. Zaleski, which is common on foodstuffs in Balkan regions that are notable for their history of endemic nephropathy, has been shown experimentally to cause a striking histopathological renal change in rats that are given feed contaminated by this fungus. The nephrotoxic agent(s) are only partially characterized. The principal change seen in the cortico-medullary region is karyocytomegaly, but apoptosis, identified with the ApopTag® methodology, is the first response to a dietary extract of P. polonicum-molded wheat after a few days of exposure. Chromatin debris migrates along the nephrons into the medulla, but whether the damaged epithelial fate is via autophagy is unclear. In intermittent exposure experiments, renal apoptosis was resolved with the cessation of exposure and was restored with renewed exposure. Apoptosis became less evident after 3 months of chronic exposure. In contrast, a relatively high dose of dietary ochratoxin A, a potent nephrocarcinogen in male rats after many months of dietary exposure, gave no evidence of apoptosis in asymptomatic weanlings over a few days of dietary exposure. This was attributed to a masking effect by concomitant marked histological disruption in renal tissue. However, in young adults, renal apoptosis was a primary outcome of dietary exposure to either the P. polonicum extract or to ochratoxin A, but the histopathological response to the former was less distorted. The apparent conflicted use in the literature of P. polonicum as a descriptor is highlighted.

A new cytotoxic indole alkaloid from the fungus Penicillium polonicum TY12.

A new dimeric monoterpene indole alkaloid polonidine A (1), along with five known compounds, cyclopenol (2), verrucosidin (3), fructigenine A (4), 3-O-methylviridicatin (5) and aurantiomides C (6), were isolated from Penicillium polonicum TY12. Their structures were established on the basis of extensive spectroscopic analyses. Compound 1 exhibited moderate cytotoxic activities and moderate antibacterial activity against Bacillus subtilis with MIC of 4.0 µg/mL.

Two new compounds from a mangrove sediment-derived fungus Penicillium polonicum H175.

Two new compounds, 6-acetyl-4-methoxy-3,5-dimethyl-2H-pyran-2-one (1) and (2E,4E)-5-((2S,3S,4R,5R)-3,4-dihydroxy-2,4,5-trimethyltetrahydrofuran-2-yl)-2,4-dimethylpenta-2,4-dienal (2), and 22 known compounds were identified from the mangrove-forest-derived fungus Penicillium polonicum H175. The structures of these compounds were elucidated by analysis of the high-resolution electrospray ionisation mass spectroscopy (HR-ESI-MS), 1 D and 2 D nuclear magnetic resonance (NMR) data. The hypoglycaemic effect of compounds was evaluated by the Tg (Ins: htBidTE-ON; LR) zebrafish model. Compound 3 (aspterric acid) exhibited a significant hypoglycaemic effect equivalent to the positive drug rosiglitazone (RSG) at 10 µmol/L.

Production, bioprocess optimization and γ-irradiation of Penicillium polonicum, as a new Taxol producing endophyte from Ginko biloba.

Twenty-eight fungal endophytes were recovered from the different parts of Ginkgo biloba and screened for their Taxol producing potency. Among these isolates, Penicillium polonicum AUMC14487 was reported as the potent Taxol producer (90.53 µg/l). The chemical identity of the extracted Taxol was verified from the TLC, HPLC, NMR, EDX, and FTIR analyses. The extracted Taxol displayed a strong antiproliferative activity against HEPG2 (IC50 4.06 µM) and MCF7 (IC50 6.07 µM). The yield of Taxol by P. polonicum was optimized by nutritional optimization with the Response Surface Methodology (RSM) using Plackett-Burman and Central Composite Designs. In addition to nutritional optimization, the effect of γ-irradiation of the spores of P. polonicum on its Taxol producing potency was evaluated. The yield of Taxol by P. polonicum was increased via nutritional optimization by response surface methodology with Plackett-Burman and FCCD designs, and γ-irradiation by about 4.5 folds, comparing to the control culture. The yield of Taxol was increased by about 1.2 folds (401.2 µg/l) by γ -irradiation of the isolates at 0.5-0.75 kGy, comparing to the control cultures (332.2 µg/l). The highest Taxol yield was obtained by growing P. polonicum on modified Czapek's- Dox medium (sucrose 40.0 g/l, malt extract 20.0 g/l, peptone 2.0 g/l, K2PO4 2.0 g/l, KCl 1.0 g/l, NaNO3 2.0 g/l, MgSO4. 5H2O 1.0 g/l) of pH 7.0 at 30.0 °C for 7.0 days. From the FCCD design, sucrose, malt extract and incubation time being the highest significant variables medium components affecting the Taxol production by P. polonicum.

Penpolonin A-E, cytotoxic α-pyrone derivatives from Penicillium polonicum.

Five new α-pyrone derivatives, named penpolonin A-E (1-5), together with two known compounds (6-7) were acquired from the endophytic fungus Penicillium polonicum isolated from the roots of Camptotheca acuminata Decne. Their structures were established by combination of NMR and HRESIMS data and the absolute configurations of 1-5 were determined by NMR calculations and comparison of experimental and calculated ECD data. Compounds 3 and 7 exhibited moderate cytotoxicity against Hep-2, TU212 human laryngeal cancer cells with IC50 values ranging from 31.6 to 45.1 µg/ml, compound 4 showed weak cytotoxicity against the Hep-2 and TU212 cell lines with IC50 values of 69.2 and 68.7 µg/ml.

Bioactive compounds derived from the marine-derived fungus MCCC3A00951 and their influenza neuraminidase inhibition activity in vitro and in silico.

Penicillium polonicum MCCC3A00951 is a fungus with influenza neuraminidase (NA) inhibition activity derived from a sediment of the mangrove forest of Zhangjiangkou in Fujian province, China. Chemical investigation on an ethyl acetate extract of its fermentation led to the isolation of a new compound, 7-hydroxy-3,10-dehydrocyclopeptine (1), and 13 known compounds (2-14). The new compound was comprehensively characterised by high-resolution electrospray ionisation-mass spectrometry, and 1D, 2D nuclear magnetic resonance (NMR) spectra. The anti-influenza NA assay was performed to evaluate the potential biological activity. Surprisingly, Cyclopenin (2) showed potent influenza NA inhibition with an IC50 value of 5.02 µM. Besides, molecular docking simulation was performed to investigate the binding model of cyclopenin (2) with influenza NA. Consequently, cyclopenin (2) could be further optimised to be a potential anti-influenza NA candidate.

Absolute Configurations and Chitinase Inhibitions of Quinazoline-Containing Diketopiperazines from the Marine-Derived Fungus Penicillium polonicum.

Three new quinazoline-containing diketopiperazines, polonimides A-C (1-3), along with four analogues (4-7), were obtained from the marine-derived fungus Penicillium polonicum. Among them, 2 and 4, 3 and 5 were epimers, respectively, resulting the difficulty in the determination of their configurations. The configurations of 1-3 were determined by 1D nuclear overhauser effect (NOE), Marfey and electron circular dichroism (ECD) methods. Nuclear magnetic resonance (NMR) calculation with the combination of DP4plus probability method was used to distinguish the absolute configurations of C-3 in 3 and 5. All of 1-7 were tested for their chitinase inhibitory activity against OfHex1 and OfChi-h and cytotoxicity against A549, HGC-27 and UMUC-3 cell lines. Compounds 1-7 exhibited weak activity towards OfHex1 and strong activity towards OfChi-h at a concentration of 10.0 µM, with the inhibition rates of 0.7%-10.3% and 79.1%-95.4%, respectively. Interestingly, 1-7 showed low cytotoxicity against A549, HGC-27 and UMUC-3 cell lines, suggesting that good prospect of this cluster of metabolites for drug discovery.

Two new compounds of Penicillium polonicum, an endophytic fungus from Camptotheca acuminata Decne.

To discover novel structural compounds which are producted by endophytic fungi, a primary chemical profiling of Camptotheca acuminata Decne derived endophytic fungus Penicillum polonicum had been taken. Two new compounds ß-lactone polonicin A (1) and enoic acid polonicin B (2) together with seven known compounds 3-9 were isolated from Penicillum polonicum obtained from C. acuminata. The structures of the new compounds 1 and 2 were identified by modern spectrum technology including detailed 1D, 2D NMR and MS data analyses. When tested against HepG2 hepatocellular carcinoma (HCC) cell lines, compounds 4-8 showed moderate anti-HCC activity. In addition, compound 1-3 have effects on increasing GLUT4 translocation and glucose uptake in vitro. Compound 1 showed the strongest glucose uptake and GLUT4 translocation activities in rat skeleton (L6) myoblast cell line with enhancements of 1.8 and 2.1 folds respectively compared to the control.

Imaging mass spectrometry-guided fast identification of antifungal secondary metabolites from Penicillium polonicum.

The discovery of antibiotics from microorganisms using classic bioactivity screens suffers from heavy labor and high re-discovery rate. Recently, largely uncovered biosynthetic potentials were unveiled by new approaches, such as genetic manipulation of "silent" biosynthetic gene clusters, innovative data acquisition, and processing methods. In this work, a fast and efficient antibiotic identification pipeline based on the MALDI-TOF imaging mass spectrometry was applied to study the antifungal metabolites during the confrontation of two fungal species, Penicillium polonicum and wilt-inducing fungus Fusarium oxysporum. By visualizing the spatial distribution of metabolites directly on the microbial colony and surrounding media, we predicted the antifungal candidates before isolating pure compounds and individually testing their bioactivity, which subsequently guided the identification of target molecules using classic chromatographic methods. Via this procedure, we successfully identified two antifungal metabolites, fructigenine A and B, which belong to indole alkaloid class and were not reported for antifungal activity. Our work assigned new bioactivity to previously reported compounds and more importantly showed the efficiency of this approach towards quick discovery of bioactive compounds, which can help study the vast unexploited synthetic potential of microbial secondary metabolites.

Efficient visible light induced synthesis of silver nanoparticles by Penicillium polonicum ARA 10 isolated from Chetomorpha antennina and its antibacterial efficacy against Salmonella enterica serovar Typhimurium.

The green synthesis of silver nanoparticles (AgNPs) using biological systems such as fungi has evolved to become an important area of nanobiotechnology. Herein, we report for the first time the light-induced extracellular synthesis of silver nanoparticles using algicolous endophytic fungus Penicillium polonicum ARA 10, isolated from the marine green alga Chetomorpha antennina. Parametric optimization, including the concentration of AgNO3, fungal biomass, ratio of cell filtrate and AgNO3, pH, reaction time and presence of light, was done for rapid AgNPs production. The obtained silver nanoparticles (AgNPs) were characterized by UV-Visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy and Transmission electron microscopy (HRTEM-EDAX). The AgNPs showed a characteristic UV-visible peak at 430 nm with an average size of 10-15 nm. The NH stretches in FTIR indicate the presence of protein molecules. The Raman vibrational bands suggest that the molecules responsible for the reduction and stability of AgNPs were extracellular proteins produced by P.polonicum. Antibacterial evaluation of AgNPs against the major foodborne bacterial pathogen Salmonella enterica serovar Typhimurium MTCC 1251, was assessed by well diffusion, Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assay. Killing kinetic studies revealed complete killing of the bacterial cells within 4 h and the bactericidal nature of synthesized nanoparticles was confirmed by fluorescent microscopy and scanning electron microscopy. Furthermore, the bactericidal studies with Transmission electron microscopy (TEM) at different time intervals explored the presence of AgNPs in the cell wall of S.Typhimurium at about 30 min and the complete bacterial lysis was found at 24 h. The current research opens an insight into the green synthesis of AgNPs and the mechanism of bacterial lysis by direct damage to the cell wall.

Green synthesized silver nanoparticles by marine endophytic fungus Penicillium polonicum and its antibacterial efficacy against biofilm forming, multidrug-resistant Acinetobacter baumanii.

Acinetobacter baumanii, a gram-negative, non-motile, encapsulated coccobacillus which causes infections worldwide. The objective of this study was to find a fungal strain that could be utilized to biosynthesize antibacterial silver nanoparticles (AgNPs) against Acinetobacter baumanii. The present investigation explains rapid and extracellular biosynthesis of silver nanoparticles by the algicolous endophytic fungus, Penicillium polonicum, isolated from the marine green alga Chetomorpha antennina. The obtained silver nanoparticles were characterized by UV-Vis spectroscopy, Raman spectroscopy, Fourier transformation infrared (FTIR), and Transmission electron microscopy (TEM). The SNPs showed a characteristic UV- visible peak at 430 nm with an average size of 10-15 nm. As evident from the FTIR and Raman spectra, possibly the protein components of fungal extract have caused the reduction of silver nitrate. Parametric optimization, including the concentration of AgNO3, ratio of cell filtrate and AgNO3, fungal biomass, reaction time, pH, and presence of light, was done for rapid AgNPs production. The antibacterial efficacy of AgNPs against multi-drug-resistant, biofilm-forming Acinetobacter baumanii, was evaluated by well diffusion assay. The Minimum inhibitory concentration (MIC) of AgNP was 15.62 µgml-1 and the minimum bactericidal concentration (MBC) was 31.24 µgml-1. Killing kinetic assay revealed complete killing of the bacterial cells within 6 h. Log reduction and percent survival of bacterial cells were analyzed from killing kinetic study. Bactericidal nature of synthesized nanoparticles was confirmed by fluorescent microscopical analysis. The effect of AgNPs on the ultrastructure of bacterial pathogen was evaluated by Transmission electron microscopy.

A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1.

Four quinolinones (1-4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. In addition, five new quinolinone derivatives (5-9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 µg/mL and 30.7 µg/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.

Comments on "Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China. Toxins 2015, 7, 3858-3875"- in Attributing Ochratoxin A Biosynthesis Within the Genus Penicillium Occurring on Natural Agricultural Produce.

The unusual attribution of trace amounts of ochratoxin A in some Chinese food commodities to Penicillium polonicum is questioned by European experience in searches for ochratoxinogenic food-spoilage Penicillia, where mistaken attribution is now known to have been due to cryptic Penicillium verrucosum contamination. Consequently, selection of single-spore isolates is recommended as pre-requisite for attributing mycotoxin biosynthetic potential to fungi.