The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was found to grow vigorously in an intact Pinus koraiensis seed, it is inferred that the strain may develop unique mechanisms associated with the biosynthesis of rare metabolites. Further fermentation of the strain on solid rice medium yielded thirteen undescribed compounds, including three andrastin-type meroterpenoids (1-3), two α- pyrone polyketides (4 and 5), and eight sesquicarane derivatives (6-13), along with seven known compounds (14-20). Their structures were determined by detailed analysis of the spectroscopic and spectrometric data (NMR and HRESIMS), in addition to comparisons of the experimental and calculated ECD data for absolute configurational assignments. The hemiacetal moiety in compounds 1 and 2 and the 3α-hydroxy group in compound 3 were rarely found in the andrastin-type meroterpenoid family. The sesquicaranes belong to a small group of sesquiterpenoid that are rarely reported. Bioassay study showed that compound 1 exhibited inhibitory effects against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 with MIC values of 64 and 32 μg/mL, respectively. In addition, compounds 1 and 3 displayed weak DPPH radical scavenging activities. The andrastins and sesquicaranes in this study enriched the structural diversity of these classes of terpenoids. Of note, this study is the first report on the metabolites of a fungus isolated from P. koraiensis seed.

Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2-7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1-7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

One new rare carbon-bridged citrinin dimer quinocitrindimer C (1) as a pair of epimers, two new polyketide penicilliodes D (3) and E (4) together with nine known citrinin derivatives, were isolated from the fermentation broth of starfish-derived symbiotic fungus Penicillium sp. GGF16-1-2. Their structures and configurations were elucidated by comprehensively spectroscopic data analysis and electronic circular dichroism calculations. Eleven citrinin derivatives were tested by Colletotrichum gloeosporioides, and compound 2 played a significant antifungal activity against Colletotrichum gloeosporioides with LC50 value of 0.27 μg/ml.

An eleven-year-old Pit Bull Terrier was presented to the veterinary practice with an acute onset of whole-body seizures. The clinical signs developed in a garden where the dog was kept that morning. There was a suspicion of tremorgenic mycotoxin poisoning by compost as the dog had vomited parts of compost right before the onset of the seizures and there was a pile of compost located in the garden. The dog underwent immediate decontamination following supportive treatment and recovered fully within 24 h of intensive care. The samples of the vomit and parts of the compost were cultivated. In the sample of the vomit, Penicillium sp. was found. Subsequently, tremorgenic mycotoxins paxilline, penitrem A and roquefortine C were determined chromatographically at significant concentrations in the vomit and a growth medium with cultivated Penicillium sp. The aim of this work is to describe the complex therapeutic and diagnostic approach to the patient with a suspected tremorgenic mycotoxin poisoning where a combination of mycological and chromatographic analyses was used to confirm the diagnosis. To the best of our knowledge, this is the first confirmed case of canine tremorgenic mycotoxicosis in the Czech Republic and the first reported case of paxilline poisoning in a dog.

Chemical investigation of Penicillium sp. GDGJ-N37, a Sophora tonkinensis-associated fungus, yielded two new azaphilone derivatives, N-isoamylsclerotiorinamine (1) and 7-methoxyl-N-isoamylsclerotiorinamine (2), and four known azaphilones (3-6), together with two new chromone derivatives, penithochromones X and Y (7 and 8). Their structures were elucidated based on spectroscopic data, CD spectrum, and semi-synthesis. Sclerotioramine (3) showed significant antibacterial activities against B. subtilis and S. dysentery, and it also showed most potent anti-plant pathogenic fungi activities against P. theae, C. miyabeanus, and E. turcicum.

In our chemical investigation into Penicillium sp. UJNMF0740 derived from mangrove sediment, fourteen indole diterpene analogs, including four new ones, are purified by multiple chromatographic separation methods, with their structures being elucidated by the analyses of NMR, HR-ESIMS, and ECD data. The antibacterial and neuroprotective effects of these isolates were examined, and only compounds 6 and 9 exhibited weak antibacterial activity, while compounds 5, 8, and 10 showed protective effects against the injury of PC12 cells induced by 6-hydroxydopamine (6-OHDA). Additionally, compound 5 could suppress the apoptosis and production of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells as well as trigger the phosphorylation of PI3K and Akt. Taken together, our work enriches the structural diversity of indole diterpenes and hints that compounds of this skeleton can repress the 6-OHDA-induced apoptosis of PC12 cells via regulating the PI3K/Akt signaling pathway, which provides evidence for the future utilization of this fascinating class of molecules as potential neuroprotective agents.

In this bioremediation study, the fungus Penicillium sp. isolated from kefir grains was evaluated for its resistance to copper in the culture medium. Penicillium sp. was cultivated in liquid medium prepared using 2% malt-agar at pH 7.0. Biomass of the fungus was significantly reduced, but only when 800 mg·L-1 of Cu(NO3)2 copper nitrate was used. The effect on radial growth of the fungus in experiments combining different pH values and the inorganic contaminant showed an inhibition of 73% at pH 4.0, 75% at pH 7.0 and 77% at pH 9.0 in liquid medium. Thus, even though the growth of Penicillium sp. could be inhibited with relatively high doses of copper nitrate, images obtained with scanning electron microscopy showed the preservation of fungal cell integrity. Therefore, it can be concluded that Penicillium sp. isolated from kefir grains can survive while performing bioremediation to minimize the negative effects of copper on the environment through biosorption.

The biopolymer melanin is reported for many biological processes to secure biological entities over unfavorable environmental factors. The present study aimed to isolate soil fungi and screen for melanin production. The potent fungus was identified as Penicillium citrinum NP4 based on morphological and molecular characterization with accession number OP070954. Using standardized tyrosine broth conditions melanin was produced by NP4 and extracted by acidification. Extracted melanin exhibited maximum UV-visible absorption at 223 nm; FTIR peaks validate the occurrence of CO, CN, CH, and CC functional groups present in the indole/pyrrole structure. TLC analysis exhibited a prominent single band with a Retardation factor (Rf) of 0.68, resonance peaks at 6.621, 7.061, and 7.185 ppm exhibited aromatic hydrogen in the indole/pyrole system in 1H NMR. The EDX peaks confirm the presence of carbon, oxygen, sulfur, and nitrogen elements which are the key factors in melanin structure, and TGA reports the thermal stability of the melanin. An in silico molecular docking approach on lung cancer causing proteins EGFR (3g5z), KRAS (6vc8), and TP53 (8 dc4) were conducted to determine the active binding sites of the melanin, and proteins exhibited binding affinity of -8.0 for 3g5z, -9.8 for 6vc8, and - 10.1 kcal/mol for TP53 protein with melanin. Anticancer activity of the melanin showed significant inhibition of A549 cells in dose-dependent mode with significant IC50 of 65.49 μg/mL; apoptotic examination reveals 46.14 % apoptosis for melanin and 46.36 % apoptosis for standard drug (cisplatin). Melanin exhibited good photoprotection capacity at 1 μg/mL. In conclusion, the extracted melanin exhibited significant results on many biological applications and it can be used in the pharmaceutical field to avoid chemical-based drugs.

The production and use of dibutyl phthalate (DBP) are increasing, and the resulting health and environmental problems are of concern. Therefore, the present study focused on the biodegradation of DBP in liquid fermentation using endophytic Penicillium species and evaluated the cytotoxic, ecotoxic, and phytotoxic effects of the fermented filtrate (by-product). Higher biomass yield was observed in fungal strains grown in DBP-containing media (DM) compared to DBP-free (control) media (CM). The highest esterase activity was observed at 240 h during fermentation with Penicillium radiatolobatum (PR) grown in DM (PR-DM). As per gas chromatography/mass spectrometry (GC/MS) results, the PR degraded 99.986 % of DBP after 288 h of fermentation. Furthermore, compared to DM treatment, the fermented filtrate of PR-DM demonstrated negligible toxicity in HEK-293 cells. Besides, the treatment of PR-DM in Artemia salina indicated >80 % viability and showed a trivial ecotoxic effect. However, compared to the control, the fermented filtrate of PR-DM treatment resulted in ~90 % of the roots and shoots growth of Zea mays seeds, indicating no phytotoxicity. Overall, the findings of this study suggested that PR can degrade DBP in liquid fermentation without generating toxic byproducts.