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Four new polyketides, namely furantides A-B ( 1 - 2 ), talamin E ( 3 ) and arugosinacid A ( 4 ), and two known polyketides were obtained from the mangrove-derived fungus Penicillium sp. HDN15-312 using the One Strain Many Compounds (OSMAC) strategy. Their chemical structures, including configurations, were elucidated by detailed analysis of extensive NMR spectra, HRESIMS and ECD. The DPPH radicals scavenging activity of 3 , with an IC 50 value of 6.79 µM, was better than vitamin C.

Crosstalk-oriented chemical evolution of natural products (NPs) is an efficacious strategy for generating novel skeletons through coupling reactions between NP fragments. In this study, two NOD-like receptor protein 3 (NLRP3) inflammasome inhibitors, sorbremnoids A and B ( 1 and 2 ), with unprecedented chemical architectures were identified from a fungus Penicillium citrinum . Compounds 1 and 2 exemplify rare instances of hybrid NPs formed via a major facilitator superfamily (MFS)-like enzyme by coupling reactive intermediates from two separate biosynthetic gene clusters (BGCs), pcisor and pci56 . Both sorbremnoids A and B are NLRP3 inflammasome inhibitors. Sorbremnoid A demonstrated strong inhibition of IL-1β by directly binding to the NLRP3 protein, inhibiting the assembly and activation of the NLRP3 inflammasome in vitro , with potential application in diabetic refractory wound healing through the suppression of excessive inflammatory responses. This research will inspire the development of anti-NLRP3 inflammasome agents as lead treatments and enhance knowledge pertaining to NPs derived from biosynthetic crosstalk.

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.

Six new α-pyrone polyketides, penipyrols C-G (1-5) and methyl-penipyrol A (6), together with one biogenetically related known compound, penipyrol A (7), were isolated from the extract of fungus Penicillium sp. HDN-11-131. Their structures including the absolute configurations were established by extensive spectroscopic analysis, Mosher's method, and ECD calculations as well as biogenic considerations. Compounds 1-4 possess a rare skeleton featuring γ-butyrolactone linked to α-pyrone ring through double bond. Compound 1 can induce pancreatic β-cell regeneration in zebrafish at 10 μM, which demonstrated promising anti-diabetes potential., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Eight new dioxopiperazine alkaloids, penispirozines A-H ( 1 - 8 ), were discovered from the mangrove-derived fungus Penicillium janthinellum HDN13-309. Their structures were elucidated by spectroscopic analysis, TDDFT-ECD calculations, and X-ray diffraction. Compound 1 had an unusual pyrazino[1,2]oxazadecaline coupled with a thiophane ring system, and compound 2 possessed a 6/5/6/5/6 pentacyclic ring system with two rare spirocyclic centers. Interestingly, compounds 3 - 8 were distinguished by not only the existence of a spiro -thiophane or spiro -furan ring system but also the chirality of the pentacyclic moiety. Compounds 3 and 4 increased the expression of the two relevant phase II detoxifying enzymes SOD2 and HO-1 at 10 μM.

Three new polyketides, ketidocillinones A-C ( 1 - 3 ), were discovered from the extract of an Antarctica sponge-derived fungus Penicillium sp. HDN151272. All the structures were deduced by spectroscopic data, including NMR and HRESIMS. The absolute configuration of compound 3 was established by using ECD calculation. Compounds 1 - 3 can be slowly oxidized to quinone form when exposed to air. Ketidocillinones B and C ( 2 and 3 ) exhibited potent antibacterial activity against Pseudomonas aeurigenosa , Mycobacterium phlei, and MRCNS (methicillin-resistant coagulase-negative staphylococci ) with MIC values ranging from 1.56 to 25.00 µg/mL., Competing Interests: The authors declare no conflict of interest.

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide ( 1 ) and 10,11,16,17-tetrahydrobislongiquinolide ( 2 ), as well as four known analogues, bislongiquinolide ( 3 ), 16,17-dihydrobislongiquinolide ( 4 ), sohirnone A ( 5 ), and 2',3'-dihydrosorbicillin ( 6 ). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds.

Four new alkyl aromatics, penixylarins A-D ( 1 - 4 ), along with the known biogenetically related 1,3-dihydroxy-5-(12-hydroxyheptadecyl)benzene ( 5 ) and 1,3-dihydroxy-5-(12-sulfoxyheptadecyl)benzene ( 6 ), were isolated from a mixed culture of the Antarctic deep-sea-derived fungus Penicillium crustosum PRB-2 and the mangrove-derived fungus Xylaria sp. HDN13-249. UPLC-MS data and an analysis of structural features showed that compounds 1 and 2 were produced by collaboration of the two fungi, while compounds 3 - 6 could be produced by Xylaria sp. HDN13-249 alone, but in noticeably increased quantities by cocultivation. Compounds 2 , 3 , 5 , and 6 showed antibacterial activity against a panel of strains, and compound 3 possessed potential antituberculosis effects (MIC = 6.25 μM against Mycobacterium phlei ).

Seven new polyketides, named tanzawaic acids R-X ( 1 - 6 , 11 ), along with seven known analogues ( 7 - 10 and 12 - 14 ), were isolated from Penicillium steckii HDN13-279. Their structures, including the absolute configurations, were elucidated by NMR, MS, X-ray diffraction, circular dichroism (CD) analyses and chemical derivatization. Five compounds ( 2 , 3 , 6 , 10 and 12 ) significantly decreased the oleic acid (OA)-elicited lipid accumulation in HepG2 liver cells at the concentration of 10 μM, among which, four compounds ( 3 , 6 , 10 and 12 ) significantly decreased intracellular total cholesterol (TC) levels and three Compounds ( 3 , 6 , and 10 ) significantly decreased intracellular triglyceride (TG) levels. Moreover, the TG-lowering capacities of compounds 6 and 10 were comparable with those of simvastatin, with the TG levels being nearly equal to blank control. This is the first report on the lipid-lowering activity of tanzawaic acid derivatives., Competing Interests: The authors declare no conflict of interest.

Four new polyketides, penitalarins A-C (1-3) and nafuredin B (4), together with the known biogenetically related nafuredin A (5) were isolated from a mixed culture of a deep-sea-derived fungus Talaromyces aculeatus and a mangrove-derived fungus Penicillium variabile. Liquid chromatography/mass spectrometry analysis showed that none of compounds 1-5 was produced by either of the two fungi when cultured alone under the same condition. The structures of 1-4, including absolute configurations, were deduced based on the interpretation of MS, NMR data, and time-dependent density functional theory calculations of specific electronic circular dichroism spectra. Compounds 1-3 possess a 3,6-dioxabicyclo[3.1.0]hexane ring, and 4 showed cytotoxicity with IC 50 values ranging from 1.2 to 9.8 μM against a panel of human cancer cell lines.

Abstract: Three novel carbon-bridged citrinin dimers, dicitrinones A–C (1–3), were isolated from a volcano ash-derived fungus Penicillium citrinum. Their structures were elucidated by spectroscopic methods. Dicitrinone A (1) and B (2) are two atropisomeric mixtures, which were verified by both NMR and quantum chemical calculations. Their cytotoxicity against four tumor cell lines (HL-60, MOLT-4, A-549, and BEL-7402) was evaluated by SRB and MTT methods. Dicitrinone B (2) arrested the HL-60 cell cycle at the G2/M phase, which was analyzed using flow cytometry. [ABSTRACT FROM AUTHOR]

• Two new two new citrinin dimers with rare C-7/C-7′ carbon-bridges were isolated from a marine derived fungus. • Compound 2 was the first citrinin dimer consisted of two mono-benzene monomers. • Compound 1 displayed antioxidant activity. Two new citrinin dimers named dicitrinones E and F (1 and 2), together with one biogenetically related known citrinin monomer (3), were isolated from the marine derived fungus Penicillium citrinum HDN-152-088. All structures including the absolute configurations were elucidated on the basis of comprehensive spectroscopic data, and assisted by ECD calculations. Among them, compounds 1 and 2 belong to the class of citrinin dimers with a rare carbon-bridged C-7/C-7′ linkage. Compound 1 displayed antioxidant activity with IC 50 value of 23.73 μM. [ABSTRACT FROM AUTHOR]