Fungus Penicillium Sp Research Articles

Guignardones Y–Z, Antiviral Meroterpenes from Penicillium sp. NBUF154 Associated with a Crella Sponge from the Marine Mesophotic Zone

Guignardones Y-Z (1-2), two new meroterpenoids, and six known metabolites involving guignardones A-H (3-4), gyorgy-isoflavone (5), daidzein (6), blumenol A (7) and guignardianone A (8) were isolated from the fungus Penicillium sp. NBUF154, which was obtained from a 60 m deep Crella sponge. Their structures including absolute configurations were unambiguously elucidated by exhaustive spectroscopic analysis and ECD calculations. A putative biosynthetic pathway toward guignardones (1-4) is here proposed. Biological evaluation of compounds 1-8 showed that 1 and 7 exert potent inhibitory effects towards human enterovirus 71 (EV71).

Three unusual hybrid sorbicillinoids with anti-inflammatory activities from the deep-sea derived fungus Penicillium sp. SCSIO06868

Under the guidance of MS/MS based molecular networking, bisorbicillchaetones A–C, three undescribed hybrid sorbicillinoids, were isolated from cultures of the deep-sea derived fungus Penicillium sp. SCSIO06868. The planar structures and absolute configurations of these compounds were determined by extensive spectroscopic analyses. Bisorbicillchaetones are the first examples of hybrid sorbicillinoids containing a coniochaetone unit. Bisorbicillchaetones A and B exhibited moderate inhibitory effect on NO production in LPS activated RAW264.7 cells with the IC50 values of 80.3 ± 3.6 μM and 38.4 ± 3.3 μM, respectively, without cytotoxicity observed.

Rare Carbon-Bridged Citrinin Dimers from the Starfish-Derived Symbiotic Fungus Penicillium sp. GGF16-1-2.

Four novel, rare carbon-bridged citrinin dimers, namely dicitrinones G–J (1–4), and five known analogs (5–9) were isolated from the starfish-derived fungus Penicillium sp. GGF 16-1-2. Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds 1–9 exhibited strong antifungal activities against Colletotrichum gloeosporioides with LD50 values from 0.61 μg/mL to 16.14 μg/mL. Meanwhile, all compounds were evaluated for their cytotoxic activities against human pancreatic cancer BXPC-3 and PANC-1 cell lines; as a result, compound 1 showed more significant cytotoxicities than the positive control against both cell lines. In addition, based on the analyses of the protein-protein interaction (PPI) network and Western blot, 1 could induce apoptosis by activating caspase 3 proteins (CASP3).

Austin Meroterpenoids from Mangrove-Derived Fungus Penicillium sp. MGP11 with α-Glucosidase Inhibitory Activity

Austin Meroterpenoids from Mangrove-Derived Fungus Penicillium sp. MGP11 with α-Glucosidase Inhibitory Activity

Hybrid Diterpenic Meroterpenoids from an Endophytic Penicillium sp. Induced by Chemical Epigenetic Manipulation.

Cultivation of an endophytic fungus Penicillium sp. KMU18029 with suberanilohydroxamic acid (SAHA), a histone deacetylase inhibitor, led to the isolation of two pairs of diterpenic meroterpenoids with a unique natural product framework combining features of pyripyropenes and decaturins/oxalicines, pyrandecarurins A (1) and B (2), pileotin A (3) and B (4), along with their potential precursor decaturenoid (5). Compounds 1, 2, 4, and 5 were new. The structures of 1-5 were elucidated by extensive spectroscopic analyses. The absolute configurations of 1-4 were determined by single-crystal X-ray diffraction, NOESY spectra, ECD calculations, and biogenetic considerations. The absolute configuration of compound 3 was confirmed for the first time. Compound 5 showed moderate activity against AChE with an IC50 value of 13.9 ± 1.1 μM.

Two New Alkaloids from the Marine-Derived Fungus Penicillium sp. LSH-3-1.

Two new alkaloids, peniokaramine (1) and penipyranopyridine (6), along with seven known compounds, were isolated from the marine-derived fungus Penicillium sp. LSH-3-1. Their structures were elucidated from UV, IR, MS, 1D and 2D NMR spectroscopic data. The anti-inflammatory potential of compounds 1-8 in LPS-induced RAW264.7 cells was detected, revealing that compounds 3 and 5 significantly decreased LPS-induced production of pro-inflammatory mediators, including NO, IL-6 and TNF-α. Compounds 1-8 were also screened for their cytotoxic activity against A549 cells and compound 1 showed moderate activity.

Lipid-rich endo-metabolites from a vertically transmitted fungal endophyte Penicillium sp. PM031 attenuate virulence factors of phytopathogenic Ralstonia solanacearum

The bacterial wilt caused by Ralstonia solanacearum is a destructive plant disease globally. Since a completely non-biological control measure could be a matter of environmental concern, investigations of developing eco-friendly strategies are required to control this phytopathogen. Attenuation of the bacterial virulence in addition to destroying the pathogen may be an alternative and overarching approach to control this disease. In this study, we have explored the potentiality of a vertically transmitted endophytic fungus Penicillium sp. PM031 isolated from stem of in vitro grown, wilt susceptible tomato cultivar to control this phytopathogen. The endophytic fungus was unable to inhibit the bacterial growth during direct confrontation in co-culture system; rather its growth and extracellular secretion were affected by the bacterium. Interestingly, the PM031-derived endo-metabolites, containing ~80% of lipid molecules, showed the dose-dependent growth inhibitory effect against R. solanacearum. Metabolite treatment with a concentration of 2500 and 5000 μg/ml significantly inhibited the bacterial growth 24.72% and 64.31%, respectively. Higher concentrations of endo-metabolite treatment exhibited antibacterial activity by rupturing cellular membranes. Furthermore, the endo-metabolites negatively influence the virulence factors necessary in early phases of bacterial infection, such as motility and biofilm formation. Our study highlights even if an endophytic fungus associated with the susceptible host plant cannot tackle R. solanacearum directly, its lipid-rich metabolites have potential to attenuate the virulence of phytopathogen. We believe this study can be a stepping stone to develop suitable formulations to control the bacterial wilt in a sustainable way, which will reduce excessive uses of synthetic bactericides.

Secondary Metabolites from the Mangrove-Derived Fungus Penicillium sp. TGM112 and their Bioactivities

Secondary Metabolites from the Mangrove-Derived Fungus Penicillium sp. TGM112 and their Bioactivities

Tanzawaic Acids from a Deep-Sea Derived Penicillium Species.

Twelve new tanzawaic acid derivatives, penitanzacids A-F (1-6), and G-J (9-12), and hatsusamides C-D (13-14), together with two revised structures [tanzawaic acids I-J (7-8)] and three known compounds (15-17) were isolated from the deep-sea-derived fungus Penicillium sp. KWF32. Their structures including absolute configurations were elucidated by spectroscopic data analysis, HRESIMS data, modified Mosher's method, chemical degradation studies, ECD calculations, single crystal X-ray diffraction, and biogenic considerations in comparison with reported known analogues. Penitanzacids H-J (10-12) represent the first examples of this family with a C3 side chain and support the proposed biosynthetic pathway in which the side chain is connected to the decalin backbone. Hatsusamides C-D (13-14) have a hybrid skeleton formed by linking a tanzawaic acid and a diketopiperazine through an ester bond. Compounds 13 and 14 exhibit weak cytotoxicity against the A549 cell line.

Antimicrobial activity of fungi isolated from Tan Dao mangrove forest in Khanh Hoa

Mangrove-derived fungi are the potential source of novel metabolites, comprising unique molecular structures with diverse bioactivities. In this study, 32 fungal strains isolated from the Tan Dao mangrove forest in Khanh Hoa province were investigated for their ability to produce antimicrobial agents using the disc diffusion method. Seventy-eight percent of obtained fungi (25 out of 32 isolates) exhibited antimicrobial activity against at least two test pathogens. Of them, bacteria Bacillus cereus and Streptococcus faecalis were the most susceptive to the antimicrobial activity of all fungal isolates with inhibition zones ranging from 8 to 36 mm, respectively, followed by Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, and Pseudomonas aeruginosa. There were only three fungal isolates that showed antimicrobial activity towards Candida albicans with the inhibition zone of 8−17 mm diameter. The strain LM.8.1 showing significant activity against all test microorganisms was identified as Penicillium sp. LM.8.1. The effect of culture conditions including pH, salinity, and incubation time on the production of antibacterial compounds of fungus Penicillium sp. LM.8.1 was also studied. The results indicated that fungi isolated from the Tan Dao mangrove forest possess potent antimicrobial properties and should be further investigated.

Citreobenzofuran D-F and Phomenone A-B: Five Novel Sesquiterpenoids from the Mangrove-Derived Fungus Penicillium sp. HDN13-494.

Five new sesquiterpenoids, citreobenzofuran D–F (1–3) and phomenone A–B (4–5), along with one known compound, xylarenone A (6), were isolated from the culture of the mangrove-derived fungus Penicillium sp. HDN13-494. Their structures were deduced from extensive spectroscopic data, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Furthermore, the absolute structures of 1 were determined by single-crystal X-ray diffraction analysis. Citreobenzofuran E–F (2–3) are eremophilane-type sesquiterpenoids with rare benzofuran frameworks, while phomenone A (4) contains a rare thiomethyl group, which is the first report of this kind of sesquiterpene with sulfur elements in the skeleton. All the compounds were tested for their antimicrobial and antitumor activity, and phomenone B (5) showed moderate activity against Bacillus subtilis, with an MIC value of 6.25 μM.

Anti-Diabetic Indole-Terpenoids From Penicillium sp. HFF16 Isolated From the Rhizosphere Soil of Cynanchum bungei Decne.

Finding novel anti-diabetic compounds with effective suppression activities against hepatic glucagon response is urgently required for the development of new drugs against diabetes. Fungi are well known for their ability to produce new bioactive secondary metabolites. As part of our ongoing research, five new indole-terpenoids (1–5), named encindolenes D-H, were isolated from the fungus Penicillium sp. HFF16 from the rhizosphere soil of Cynanchum bungei Decne. The structures of the compounds were elucidated by spectroscopic data and ECD analysis. In the anti-diabetic activity assay, compounds 1–5 could inhibit the hepatic glucose production with EC50 values of 17.6, 30.1, 21.3, 9.6, and 9.9 μM, respectively, and decrease the cAMP contents in glucagon-induced HepG2 cells.

Xanthene and citrinin derivatives from the endophytic fungus Penicillium sp. T2-11

A new xanthene derivative penicnthene (1), a new citrinin derivative penicitrinone H (2), along with three known analogues were isolated from rice solid culture media of the endophytic fungus Penicillium sp. T2-11 through the application of one strain many compounds (OSMAC) strategy. Their structures and stereochemistry were determined by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) analysis aided by TDDFT-ECD calculations. Penicnthene (1) represented the first xanthene featuring a 3-hydroxy-2-butyl chain functionality. Compounds 1–3 were assessed for their DPPH radical scavenging, antimicrobial, acetylcholinesterase inhibitory, and cytotoxic activities. Both 1 and 2 exhibited radical scavenging activities against DPPH with potency comparable to the positive control trolox. Compound 1 showed remarkable antibacterial activity against Bacillius subtilis with MIC value of 4.0 μg/mL. 2 also displayed potent activity against Staphylococcus aureus. A putative biosynthetic pathway for compounds 1–6 were proposed.

New diketopiperazine alkaloid and polyketides from marine-derived fungus Penicillium sp. TW58-16 with antibacterial activity against Helicobacter pylori

Marine-derived fungi can usually produce structurally novel and biologically potent metabolites. In this study, a new diketopiperazine alkaloid (1) and two new polyketides (10 and 11), along with 8 known diketopiperazine alkaloids (2–9) were isolated from marine-derived fungus Penicillium sp. TW58-16. Their structures were fully elucidated by analyzing UV, IR, HR-ESI-MS, 1D, and 2D NMR spectroscopic data. The absolute configurations of the new compounds 1, 10 and 11 were ascertained by X-ray diffraction (Cu Kα radiation) and comparing their CD data with those reported. In addition, the antibacterial activities of these compounds against Helicobacter pylori in vitro were assessed. Results showed that compounds 3, 6, 8 and 9 displayed moderate antibacterial activity against standard strains and drug-resistant clinical isolates of H. pylori in vitro. This result demonstrates that diketopiperazine alkaloids could be lead compounds to be explored for the treatment of H. pylori infection.

New N-methyl-4-quinolone alkaloid and citrinin dimer derivatives from the sponge-derived fungus Penicillium sp. SCSIO 41303

Four new N-methyl-4-quinolones (1–4) and a new citrinin dimer derivative (10) with fourteen known compounds (5–9, 11–19) were isolated from the sponge-derived fungus Penicillium sp. SCSIO41303. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and X-ray single-crystal diffraction. Most of the isolated compounds were evaluated for their cytotoxic, antibacterial, anti-virus, and enzyme inhibitory activities against acetylcholinesterase (AChE), and pancreatic lipase (PL). Compounds 2 and 11 exhibited enzyme inhibition activity against PL with IC50 values of 24.6 and 7.2 μg/mL, respectively. Besides, compound 11 showed enzyme inhibition activity against AChE with IC50 value of 16.5 μg/mL. Compound 15 showed moderate inhibition activities with 52.2% at the concentration of 50 μg/mL against PL and antibacterial activity against Staphylococcus aureus displaying diameter of about 10 mm.

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14.

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.

Cytotoxic Indole-Diterpenoids from the Marine-Derived Fungus Penicillium sp. KFD28.

Four new indole-diterpenoids, named penerpenes K-N (1–4), along with twelve known ones (5–16), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus Penicillium sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound 4 represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (4, 9, and 15) were cytotoxic to cancer cell lines, of which compound 9 was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 μM. Moreover, six compounds (5, 7, 10, 12, 14, and 15) showed antibacterial activities against Staphylococcus aureus ATCC 6538 and Bacillus subtilis ATCC 6633.

Isolation of actinobacterial endophytes from wheat sprouts as biocontrol agents to control seed pathogenic fungi.

Seed-borne Streptomyces can transmit vertically from generation to generation and be a mutualism between the endosymbionts and hosts. The aim of this study was to isolate and characterize endophytic Streptomyces strains from wheat sprouts, and to investigate their protection against wheat seed pathogenic fungi Penicillium. Endophytic Streptomyces sp. F6 and Streptomyces sp. F39 were isolated from wheat sprouts germinated under sterile conditions. Both Streptomyces strains could produce siderophores, and showed antagonistic activities against the seed pathogenic fungi Penicillium sp. Z17. The inoculation of Streptomyces sp. F39 and F6 could protect wheat seed germination and promote seedling growth under Penicillium sp. Z17 infection. However, the protection efficiency was impacted by the Streptomyces spore concentrations, the concentration ratios of Streptomyces spores to pathogen spores, and inoculation methods. The results suggested that wheat sprouts harbored diverse endophytic Streptomyces species which derived from wheat seeds, these strains should be more likely transmitted to the next generation, and confer competitive ability to pathogens on the offspring. Owing to the more intimate correlation between sprout endophytic flora with host plants, these strains are more suitable for mature plant interiors compared with those from rhizosphere soils and root interiors.

Citrinin and α-pyrone derivatives with pancreatic lipase inhibitory activities from Penicillium sp. SCSIO 41302

One new citrinin monomer derivative (1), and two new natural products α-pyrone analogues (2a and 2b), were isolated from the sponge derived fungus Penicillium sp. SCSIO 41302. Their structures were determined by extensive spectroscopic analysis, chiral-phase HPLC analysis, modified Mosher’s method, ECD calculations, and X-ray single-crystal diffraction. Bioactivity screening showed that compounds 2b and 8 exhibited obvious inhibitory activities against pancreatic lipase and acetyl cholinesterase with IC50 values of 48.5 and 4.8 μM, respectively, which indicated that different chiral center between enantiomers (2a and 2b) might result in different biological activities (IC50 value against PL for 2a >100 μg/ml).

Pests and Diseases in Foxtail Millet (Setaria italica L. Beauv.) Cultivated in The Greenhouse

Greenhouse ecosystem with more stable abiotic factors could affect the population and diversity of pests and diseases found on foxtail millet (Setaria italica L. Beauv.) compared to their natural ecosystems. We observed and identified pests and diseases in seven genotypes of foxtail millet namely “Toraja”, “ICERI 5”, “ICERI 6”, “Botok 4”, “Botok 10”, “Mauliru”, and “Hambapraing”; these activities are important for the formulation of appropriate integrated pest management techniques. Using plant samples that were at the end of their vegetative phase, we found white mycelia of Fusarium incarnatum (yellowish-white colonies) and F. verticilloides (violetish-pink colonies) covering the ear-tip of the seeds and developed rapidly leading to seed rotten symptoms in “Toraja”, “ICERI 5”, and “ICERI 6”. The disease severity remained constant after these integrated management techniques were put in place. However, abnormalities in leaves leading to failure of panicle emergence occurred in “Botok 4”, “Botok 10”, “Mauliru”, and “Hambapraing”. These were caused by the fungi Penicillium sp. Identical controlling techniques were applied to this incidence and the disease incidence was reduced. Corn leaf aphids (Rhophalosiphum maidis) and rice mealybugs (Brevenia rehi) were recorded as main insect pests with severe attack. The aphid, R. maidis, colonized the stems and were associated with the sooty mold (Capnodium sp.), resulting in wilting. The mealybugs, B. rehi, colonized the flag leaves resulting in leaf rotting. Insecticide and isolating the attacked plants were used as the controlling techniques. Red-mites (Tetranychus urticae) were also detected as indicated by chlorotic spots on the upper part of the leaves. Acaricide was used to reduce its population. The pests and diseases found in the seven genotypes of foxtail millet are commonly known to occur in Poaceae. In general, greenhouse ecosystem for foxtail millet facilitated planting with high population with lower diversity of pests and diseases compared to the open field planting.