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.     

Rare C25 Steroids Produced by Penicillium chrysogenum P1X,a Fungal Endophyte of Huperzia serrata

Three new metabolites, norcyclocitrinol A ( 1 ), erythro‐11α‐hydroxyneocyclocitrinol ( 2 ), and pesudocyclocitrinol A ( 3 ), along with six known analogs, i.e., neocyclocitrinols A–D ( 4 – 7 , resp.), cyclocitrinol ( 8 ), and 24‐epicyclocitrinol ( 9 ), were isolated and identified from the culture broth of Penicillium chrysogenum P1X, a fungal endophyte of Huperzia serrata. Compounds 1 – 9 were identified by spectroscopic methods to share the same C₂₅‐steroid skeleton featuring an unusual bicyclo[4.4.1] A/B ring system. In particular, 1 represents the first example of a C₂₅ steroid with a bisnor C‐atom side chain. All compounds were evaluated for their cytotoxic activities against HeLa and HepG2 cell lines. However, none of them exhibited a significant cytotoxicity at a concentration of 20 μM .     

Biosynthesis of Bromoroquefortines in a High Saline Medium by Penicillium chrysogenum,a Terrestrial Endophyte Collected from Coffea arabica

Roquefortine C ( 1 ) and 11‐bromoroquefortine C ( 4 ) were isolated from Penicillium chrysogenum, an endophyte obtained from green leaves of Coffea arabica, during induction experiments by adding halide salts to the culture media. In our studies, 11‐bromoroquefortine D and 11‐bromo‐17‐hydroxybromoroquefortine C were identified by LC/HR‐MS. It is the first time that bromoroquefortine C and D are described as halogenated natural products. These halo alkaloids were shown to be biosynthesized from brominated tryptophan as the biosynthetic precursor. Cytotoxic and antibiotic assays using roquefortine C and 11‐bromoroquefortine C showed that the presence of the 11‐Br substituent impairs some biological activities of this alkaloid.     

Structure and absolute configuration of penicilliumine,a new alkaloid from Penicillium commune 366606

Penicilliumine (1), a new structure was isolated from the fermentation Penicillium commune 366606, a marine-derived fungus isolated from the sea water collected at Qingdao, China. HPLC chiral separation of 1 afforded two enantiomers (−)-penicilliumine and (+)-penicilliumine, respectively. The structure of 1 was established by comprehensive spectroscopic data, and single-crystal X-ray diffraction. The absolute configuration of enantiomers was determined by quantum mechanical computation of electronic circular dichroism (ECD).     

Penicillium sp.DS9701-09分泌的聚β-羟基丁酸酯(PHB)解聚酶的纯化及性质研究

以Penicillium sp.DS9701-09为研究对象,对其分泌的PHB解聚酶进行分离纯化和表征,通过超滤浓缩、硫酸铵分级沉淀和SephadexG-100凝胶过滤,从发酵液中纯化了一种对PHB具有高效降解能力的解聚酶,纯化倍数为37.9,酶活力回收率为8.9%.经SDS-PAGE检测,确定酶蛋白的相对分子质量为41.5 kDa.酶反应的最适温度和pH分别为50℃和5.0,在50℃以下和pH=5.0～6.0之间酶的稳定性较好.金属离子对PHB解聚酶具有一定的抑制作用,降解酶对PHB的酶解产物主要是羟基丁酸二聚体.     

Diketoacetonylphenalenone,Derived from Hawaiian Volcanic Soil-Associated Fungus Penicillium herquei FT729, Regulates T Cell Activation via Nuclear Factor-κB and Mitogen-Activated Protein Kinase Pathway

In immunological responses, controlling excessive T cell activity is critical for immunological homeostasis maintenance. Diketoacetonylphenalenone, derived from Hawaiian volcanic soil-associated fungus Penicillium herquei FT729, possesses moderate anti-inflammatory activity in RAW 264.7 cells but its immunosuppressive effect on T cell activation is unknown. In the present study, diketoacetonylphenalenone (up to 40 μM) did not show cytotoxicity in T cells. Western blot analysis showed treatment with diketoacetonylphenalenone did not alter the expression of anti-apoptotic proteins. Pretreatment with diketoacetonylphenalenone suppressed the interleukin-2 production in activated T cells induced by T cell receptor-mediated stimulation and PMA/A23187. The CFSE-proliferation assay revealed the inhibitory effect of diketoacetonylphenalenone on the proliferation of T cells. The expression of surface molecules on activated T cells was also reduced. We discovered the suppression of the TAK1-IKKα-NF-κB pathway by pretreatment with diketoacetonylphenalenone abrogated mitogen-activated protein kinase (MAPK) signaling in activated T cells. These results suggest that diketoacetonylphenalenone effectively downregulates T cell activity via the MAPK pathway and provides insight into the therapeutic potential of immunosuppressive reagents.     

Isolation and identification of two new compounds from the Penicillium sp. SYPF7381

Abstract

Two new compounds, (7R, 2E, 5E)-3,5,7-trimethyl-2,5-octadienedioic-8-methyl ester (1) and neovasipyridone G (3), together with a new natural product compound (7R,2E,5E)-3,5,7-trimethyl-2,5-octadienedioic acid (2), and six known compounds (4–9) were isolated from Penicillium sp. SYPF7381. Their structures were elucidated on the basis of extensive spectroscopic analysis, and the absolute configurations of compounds 1 and 2 were determined by optical rotation. The absolute configuration of compound 3 was determined by means of electronic circular dichroism (ECD) calculation. In addition, the in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. Furthermore, the structure-antiinflammation activity relationships for these isolated compounds were summarized based on the experimental as well as the docking results.     

软珊瑚Sarcophyton tortuosum共生真菌penicillium sp.的代谢产物研究

 从三亚采集的软珊瑚Sarcophyton tortuosum体内分离得到一株共生真菌Penicillium sp.,该菌在GPY培养基中培养,菌体呈浅红色。对该菌菌体的代谢产物进行了研究,纯化得到1个新化合物：(4E,6E)-2-N-十六碳酰基-1,3-二羟基十六烷-4,6-二烯-鞘胺醇 (1),以及4个已知化合物1,7-二羟基-3-甲氧基-6-甲基-蒽醌（2）,1,7,8-三羟基-3-甲氧基-6-甲基-蒽醌（3）,1-羟基-3-甲氧基-6-甲基-蒽醌（4）,4,8-二甲基-1,5-二氧环辛烷-2,6-二酮（5）。化合物结构主要通过MS,NMR等波谱数据分析确定。化合物2,3,4,5〖STBZ〗为首次从海洋真菌中分离得到。     

Purification and Biochemical Characterization of Extracellular β-Glucosidases from the Hypercellulolytic Pol6 Mutant of <Emphasis Type="Italic">Penicillium occitanis</Emphasis>

The Pol6 mutant of Penicillium occitanis fungus is of great biotechnological interest since it possesses a high capacity of cellulases and β-glucosidase production with high cellulose degradation efficiency (Jain et al., Enzyme Microb Technol, 12:691–696, 1990; Hadj-Taieb et al., Appl Microbiol Biotechnol, 37:197–201, 1992; Ellouz Chaabouni et al., Enzyme Microb Technol, 16:538–542, 1994; Ellouz Chaabouni et al., Appl Microbiol Biotechnol, 43:267–269, 1995). In this work, two forms of β-glucosidase (β-glu 1 and β-glu 2) were purified from the culture supernatant of the Pol6 strain by gel filtration, ion exchange chromatography, and preparative anionic native electrophoresis. These enzymes were eluted as two distinct species from the diethylamino ethanol Sepharose CL6B and anionic native electrophoresis. However, both behaved identically on sodium dodecyl sulfate polyacrylamide gel electrophoresis (MW, 98 kDa), shared the same amino acid composition, carbohydrate content (8%), and kinetic properties. Moreover, they strongly cross-reacted immunologically. They were active on cellobiose and pNPG with Km values of 1.43 and 0.37 mM, respectively. β-glu 1 and β-glu 2 were competitively inhibited by 1 mM of glucose and 0.03 mM of δ-gluconolactone. They were also significantly inhibited by Hg²⁺ and Cu² at 2 mM. The addition of purified enzymes to the poor β-glucosidase crude extract of Trichoderma reesei increased its hydrolytic efficiency on H₃P0₄ swollen cellulose but had no effect with P. occitanis crude extract. Besides their hydrolytic activities, β-glu 1 and β-glu 2 were endowed with trans-glycosidase activity at high concentration of glucose.     

Chloctanspirones A and B, novel chlorinated polyketides with an unprecedented skeleton, from marine sediment derived fungus Penicillium terrestre

Two novel chlorinated sorbicillinoids named chloctanspirones A (1) and B (2), possessing an unprecedented bicyclo[2.2.2]octane-2-spiro cyclohexane skeleton, together with their quasi-precursors terrestrols K (3) and L (4), two additional new chlorinated compounds, were isolated from a marine sediment derived fungus Penicillium terrestre. Their structures including absolute stereochemistries were elucidated by analysis of NMR, MS data, and TDDFT CD calculations. The cytotoxic effects of 1-4 were preliminarily evaluated in HL-60 and A-549 cells. Compound 1 was active against both HL-60 and A-549 cells with IC₅₀s 9.2 and 39.7 μM, respectively, while 2 showed weaker activity only against HL-60 cells (IC₅₀ 37.8 μM).