Fungus Penicillium Sp Research Articles

The new diketopiperazines produced by marine algicolous fungus Penicillium sp. KMM 4672

Marine fungi are a prolific source of chemically diverse biologically active metabolites [1,2]. The features of habitats of marine fungi make them very promising sources of bioactive compounds [3]. Recently cephalosporin C was the only marine fungal compound that used as a medical drug, but today fingolimod developed from myriocin is approved by FDA and EMA, and plinabulin, the synthetic derivative of diketopiperizine phenylahistin, is under phase III of clinical trials (according to clinicaltrials.gov) [4,5].

Biotransformation of 2,4-dinitroanisole by a fungal Penicillium sp.

Insensitive munitions explosives are new formulations that are less prone to unintended detonation compared to traditional explosives. While these formulations have safety benefits, the individual constituents, such as 2,4-dinitroanisole (DNAN), have an unknown ecosystem fate with potentially toxic impacts to flora and fauna exposed to DNAN and/or its metabolites. Fungi may be useful in remediation and have been shown to degrade traditional nitroaromatic explosives, such as 2,4,6-trinitrotoluene and 2,4-dinitrotoluene, that are structurally similar to DNAN. In this study, a fungal Penicillium sp., isolated from willow trees and designated strain KH1, was shown to degrade DNAN in solution within 14days. Stable-isotope labeled DNAN and an untargeted metabolomics approach were used to discover 13 novel transformation products. Penicillium sp. KH1 produced DNAN metabolites resulting from ortho- and para-nitroreduction, demethylation, acetylation, hydroxylation, malonylation, and sulfation. Incubations with intermediate metabolites such as 2-amino-4-nitroanisole and 4-amino-2-nitroanisole as the primary substrates confirmed putative metabolite isomerism and pathways. No ring-cleavage products were observed, consistent with other reports that mineralization of DNAN is an uncommon metabolic outcome. The production of metabolites with unknown persistence and toxicity suggests further study will be needed to implement remediation with Penicillium sp. KH1. To our knowledge, this is the first report on the biotransformation of DNAN by a fungus.

A new isoquinolone alkaloid from an endophytic fungus R22 of Nerium indicum

A new isoquinolone alkaloid named 5-hydroxy-8-methoxy-4-phenylisoquinolin-1(2H)-one (3), together with two known quinolinone alkaloids 3-O-methylviridicatin (1) and viridicatol (2) were isolated from the fermentation of an endophytic fungus Penicillium sp. R22 in Nerium indicum. Their structures were elucidated by NMR, IR and MS data, and were also confirmed by comparing with the reported data in the literature. Meanwhile, the antibacterial and antifungal activities of all compounds were tested, and the results showed that three compounds had strong antifungal activity. Among them, compound 2 revealed potent antibacterial activity against Staphylococcus aureus with MIC value of 15.6 μg/mL.

Three new drimane sesquiterpenoids from cultures of the fungus Penicillium sp.

Three new drimane sesquiterpenoids, 12-hydroxyalbrassitriol (1), drim-8(12)-en-6β,7α, 9α,11-tetraol (2), and drim-68(12)-dien-9α,11-diol (3), along with one known analog albrassitriol (4), were isolated from cultures of the tin mine tailings-associated fungus Penicillium sp. The new structures were determined on the basis of extensive spectroscopic analyses. All compounds were tested for their cytotoxicities against five human cancer cell lines.

Polyketides with Immunosuppressive Activities from Mangrove Endophytic Fungus Penicillium sp. ZJ-SY₂.

Nine polyketides, including two new benzophenone derivatives, peniphenone (1) and methyl peniphenone (2), along with seven known xanthones (3–9) were obtained from mangrove endophytic fungus Penicillium sp. ZJ-SY2 isolated from the leaves of Sonneratia apetala. Their structures were elucidated on the basis of MS, 1D, and 2D NMR data. Compounds 1, 3, 5, and 7 showed potent immunosuppressive activity with IC50 values ranging from 5.9 to 9.3 μg/mL.

Antimicrobial metabolites from the plant endophytic fungus Penicillium sp.

Five rare dichloro aromatic polyketides (1–5) were obtained from an endophytic fungus Penicillium sp., along with five known metabolites (6–10). Their structures were elucidated by extensive spectroscopic analysis, Mosher methods, as well as [Rh2(OCOCF3)4]-induced electronic circular dichroism (ECD) experiments. Compounds 2–4 and 6 structurally involved acyclic 1.3-diols, the uneasy configuration determinations of which were well carried out by double-derivation NMR methods. Compounds 1–10 were evaluated for their antibacterial and antifungal activities against five strains of human pathogenic microorganisms. Helvolic acid (7) showed potent inhibitory effects against Staphylococcus aureus and Pseudomonas aeruginosa with MIC (minimum inhibitory concentration) values of 5.8 and 4.6μg/mL, respectively.

Antimicrobial meroterpenoids from the endophytic fungus Penicillium sp. T2-8 associated with Gastrodia elata

A new meroterpenoid preaustinoid D (1) and a new neogrifolin derivative dihydroxyneogrifolic acid (2), together with other five previously reported meroterpenoids (3-7) were isolated from the endophytic fungus Penicillium sp. T2-8 associated with Gastrodia elata. The structures were elucidated on the basis of spectroscopic data analyses. It was the first time that neogrifolin and its derivatives were isolated from microorganism. Some of these meroterpenoids exhibited obvious antimicrobial activities in the microdilution antimicrobial assays.

Azaphilones isolated from an alga-derived fungus Penicillium sp. ZJ-27

Four new azaphilones, peniazaphilones A–D (1–4), together with four analogues (5–8), were isolated from the alga-derived fungus Penicillium sp. ZJ-27. The structures of 1–8 were elucidated by 1D and 2D NMR analysis. The absolute configurations of 1–4 were determined by electronic circular dichroism (ECD). The isolated compounds were evaluated for cytotoxic activity against two tumor cell lines and antibacterial activities against twelve aquatic pathogenic bacteria.

Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp., an endophytic fungus associated with leaves of Garcinia nobilis. The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography-mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 - 128 µg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC50 = 0.88 - 9.21 µg/mL) against HeLa cells. The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

Metabolites with Gram-negative bacteria quorum sensing inhibitory activity from the marine animal endogenic fungus Penicillium sp. SCS-KFD08.

Three new compounds named penicitor A, aculene E and penicitor B, as well as four known compounds, were isolated from the fermentation broth of Penicillium sp. SCS-KFD08 associated with a marine animal Sipunculus nudus from the Haikou bay of China. Their planar structures and absolute configurations were unambiguously elucidated by spectroscopic data, Mosher's method, CD spectrum analysis along with quantum ECD calculation. Among them, compounds 2-7 showed quorum sensing inhibitory activity against Chromobacterium violaceum CV026, and could significantly reduce violacein production in N-hexanoyl-l-homoserine lactone (C6-HSL) induced C. violaceum CV026 cultures at sub-inhibitory concentrations.

Simultaneous removal of carbon and nitrogen by mycelial pellets of a heterotrophic nitrifying fungus-Penicillium sp. L1

A novel heterotrophic nitrifying fungus, defined as Penicillium sp. L1, can form mycelial pellets in liquid medium in this study. The effects of inoculation method, C/N ratio, initial pH, and temperature were gradually evaluated to improve the simultaneous removal of total nitrogen (TN) and chemical oxygen demand (COD) in wastewater by Penicillium sp. L1. Results showed that compared with spore inoculation, 48h pellet inoculum could significantly increase the pellet size (from about 1.5mm to 3.2mm) and improve the removal capability, particularly for COD removal (from less than 50-86.20%). The removal efficiencies of TN and COD reached 98.38% (from 136.01mg/L to 2.20mg/L) and 92.40% (from 10,720mg/L to 815mg/L) under the following conditions: C/N 36, pH 3, 30°C, and inoculation with 48h pellets. The pellet diameter reached 4.8mm after 4-day cultivation. In this case, Penicillium sp. L1 removed TN from 415.93mg/L to 43.39mg/L, as well as COD from 29,533mg/L to 8850mg/L. Overall, the results indicated that the pellet size was closely related to the pollutant-removal ability of Penicillium sp. L1. Furthermore, mycelial pellets (4.8mm, dead) only adsorbed 38.08% TN (from 125.45mg/L to 77.78mg/L), which indicated that adsorption did not play a major role in the nitrogen-removal process.

An Unusual Conformational Isomer of Verrucosidin Backbone from a Hydrothermal Vent Fungus, Penicillium sp. Y-50-10.

A new verrucosidin derivative, methyl isoverrucosidinol (1), was isolated from the marine fungus Penicillium sp. Y-50-10, dwelling in sulfur rich sediment in the Kueishantao hydrothermal vents off Taiwan. The structure was established by spectroscopic means including HRMS and 2D-NMR spectroscopic analysis. The absolute configuration was defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Among hitherto known compounds with a verrucosidine backbone isolated from natural resource, compound 1 represents the first example of a new conformational isomer of its skeleton, exhibiting antibiotic activity against Bacillus subtilis with MIC value 32 μg/mL.

A New Penicitrinone Derivative from the Endophytic Fungus Penicillium sp. from Bruguiera sexangula var. rhynchopetala

Chemical investigation on the endophytic fungus Penicillium sp. B21 from the leaf of Bruguiera sexangula var. rhynchopetala led to the isolation of a new compound, penicitrinone acetate (1), the structure of which was elucidated by spectroscopic methods, including 2D NMR techniques.

Pretrichodermamides D-F from a Marine Algicolous Fungus Penicillium sp. KMM 4672.

Three new epidithiodiketopiperazines pretrichodermamides D–F (1–3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1–5 were determined based on spectroscopic methods. The absolute configuration of pretrichodermamide D (1) was established by a combination of modified Mosher′s method, NOESY data, and biogenetic considerations. N-Methylpretrichodermamide B (5) showed strong cytotoxicity against 22Rv1 human prostate cancer cells resistant to androgen receptor targeted therapies.

Bile acids from a Marine Sponge-Associated Fungus Penicillium sp.

Chemical investigation of a marine-derived fungus, Penicillium sp. 108YD020, resulted in the discovery of six bile acid derivatives, glycocholic acid (1), glycocholic acid methyl ester (2), cholic acid (3), glycochenodeoxycholic acid (4), glycodeoxycholic acid methyl ester (5), and cholic acid methyl ester (6). The structures of six bile acid derivatives 1-6 were determined by the detailed analysis of 1D, 2D NMR and LC-MS data, along with chemical methods and literature data analysis.

Exopisiod B and farylhydrazone C, two new alkaloids from the Antarctic-derived fungus Penicillium sp. HDN14-431

Two new compounds, exopisiod B (1) and farylhydrazone C (2), together with two known compounds (3–4), were isolated from the Antarctic-derived fungus Penicillium sp. HDN14-431. Their structures including absolute configurations were elucidated by spectroscopic methods and TDDFT ECD calculations. The cytotoxicity and antimicrobial activities of all compounds were tested.

Novel application assigned to toluquinol: inhibition of lymphangiogenesis by interfering with VEGF-C/VEGFR-3 signalling pathway.

Lymphangiogenesis is an important biological process associated with the pathogenesis of several diseases, including metastatic dissemination, graft rejection, lymphoedema and other inflammatory disorders. The development of new drugs that block lymphangiogenesis has become a promising therapeutic strategy. In this study, we investigated the ability of toluquinol, a 2-methyl-hydroquinone isolated from the culture broth of the marine fungus Penicillium sp. HL-85-ALS5-R004, to inhibit lymphangiogenesis in vitro, ex vivo and in vivo. We used human lymphatic endothelial cells (LECs) to analyse the effect of toluquinol in 2D and 3D in vitro cultures and in the ex vivo mouse lymphatic ring assay. For in vivo approaches, the transgenic Fli1:eGFPy1 zebrafish, mouse ear sponges and cornea models were used. Western blotting and apoptosis analyses were carried out to search for drug targets. Toluquinol inhibited LEC proliferation, migration, tubulogenesis and sprouting of new lymphatic vessels. Furthermore, toluquinol induced apoptosis of LECs after 14 h of treatment in vitro, blocked the development of the thoracic duct in zebrafish and reduced the VEGF-C-induced lymphatic vessel formation and corneal neovascularization in mice. Mechanistically, we demonstrated that this drug attenuates VEGF-C-induced VEGFR-3 phosphorylation in a dose-dependent manner and suppresses the phosphorylation of Akt and ERK1/2. Based on these findings, we propose toluquinol as a new candidate with pharmacological potential for the treatment of lymphangiogenesis-related pathologies. Notably, its ability to suppress corneal neovascularization paves the way for applications in vascular ocular pathologies.

New analogues of brefeldin A from sediment-derived fungus Penicillium sp. DT-F29

Four new analogues of brefeldin A named 7, 7-dimethoxybrefeldin C (3), 6β-hydroxybrefeldin C (4), 4-epi-15-epi-brefeldin A (5), 4-epi-8α-hydroxy-15-epi-brefeldin C (6), together with four known analogues (1, 7−9) were isolated from a fermentation of the sediment-derived fungus Penicillium sp. DT-F29. The structures of these compounds were elucidated on the basis of extensive spectroscopic and chemical methods. In the bioactivity assays, only compounds 1 and 8 showed significant inhibitory activities against human lung adenocarcinoma cell. In addition, compound 1 was first reported for the potent ability to reactivate latent HIV with EC50 value of 0.03 μM.

Bioactive α-pyrone meroterpenoids from mangrove endophytic fungus Penicillium sp.

Five α-pyrone meroterpenoids, including one new 3-epiarigsugacin E (1) and four known compounds, arisugacin D (2), arisugacin B (3), territrem C (4) and terreulactone C (5) were obtained from the marine fungus Penicillium sp. SK5GW1L. Their structures were identified by MS and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low temperature (150 K) single crystal X-ray diffraction with Cu Kα radiation. Compounds 3, 4 and 5 showed strong inhibitory activities against acetylcholinesterase (AchE) with IC50 values of 3.03, 0.23 and 0.028 μM, respectively.

Extracellular production and characterization of red pigment from Penicillium purpurogenum BKS9

Fifteen fungal species were isolated from waste soil and used for the production of red pigment. Among the fifteen fungal isolates only Penicillium sp. BKS 9 displayed excellent production ability of red pigment in sabouraud’s dextrose agar medium as well as broth medium. After 28S rRNA sequencing the fungus Penicillium sp. BKS9 was identified as Penicillium purpurogenum and submitted to NCBI (Gene Bank) with Gene Bank accession number KT222270. Further, optimization of incubation period and pH was performed and it was concluded that an incubation for 18 days with pH 6.0 at 30°C are the most favorable conditions for biomass (0.877 g/50 ml) and red pigment (0.79 Abs/ml) production. The pigment used for the study was soluble in all the organic solvents taken. The effect of red pigment on germination of fifty numbers of viable and healthy seeds of Cicer arietinum was studied and confirmed that the pigment has no significant negative effect on the germination of the seeds.