Rugulosuvines A and B--diketopiperazine alkaloids from Penicillium rugulosum and Penicillium piscarium fungi]

Two diketopiperazine alkaloids, rugulosuvines A and B (tryptophan and phenylalanine are precursors), were isolated and purified from the culture liquid of Penicillium rugulosum VKM F-352 and Penicillium piscarium VKM F-325 fungi. Physical and physicochemical studies showed the absolute structure of rugulosuvine A. The absolute structure of rugulosuvine B was demonstrated to be similar to that of rugulosuvine A.     

The Penicillium commune Thom and Penicillium clavigerum Demelius Fungi Producing Fumigaclavines A and B

The type strains Penicillium clavigerum VKM F-447 and P. commune VKM F-3233 are found to produce fumigaclavines A and B. Of the seven other strains of these species, only two strains, P. commune VKM F-3088 and F-3491, possess the ability to synthesize these alkaloids. It is suggested that the five other strains under study either lost such an ability or require very specific conditions for the synthesis of these alkaloids.     

Formation of alkaloids from Penicillium species fungi during growth on wheat kernels

The ability to produce alkaloids has been studied in 13 strains belonging to 10 species of the genus Penicillium. Most of these strains produce identical ranges of alkaloids when grown on wheat grain and synthetic Abe medium. They are roquefortine, 3,12-dihydroroquefortine, and glandicolines A and B in strain P. chrysogenum VKM F-1987; fumigaclavines A and B, festuclavine, and pyroclasine in P. commune VKM F-308, F-3491, and KBP4; agroclavine 1 and epoxyagroclavine 1 in P. fellutanum VKM F-1073; fellutanine A in P. fellutanum F-3020; roquefortine, 3,12-dihydroroquefortine, meleagrin, and glandicolines A and B in P. glandicola VKM F-743; aurantioclavine in P. nalgiovense VKM F-229; isofumigaclavines A and B, festuclavine, roquefortine, and 3,12-dihydroroquefortine in P. roquefortii VKM F-2389; roquefortine, 3,12-dihydroroquefortine, and meleagrin in P. vitale VKM F-3624; roquefortine and oxaline in P. vulpinum VKM F-256; and alpha-cyclopiazonic acid and rugulovasine B in P. viridicatum C-47. No alkaloids were found in P. rugulosum VKM F-352 grown on wheat grain. A simple method is proposed for isolating alkaloids from affected grains.     

The Penicillium commune Thom and Penicillium clavigerum Demelius fungi--fumigaclavines A and B producers

The type strains Penicillium clavigerum VKM F-447 and P. commune VKM F-3233 are found to produce fumigaclavines A and B. Of the seven other strains of these species, only two strains, P. commune VKM F-3088 and F-3491, possess the ability to synthesize these alkaloids. It is suggested that the five other strains under study either lost such an ability or require very specific conditions for the synthesis of these alkaloids.     

Production of Alkaloids by Fungi of the Genus PenicilliumGrown on Wheat Grain

The ability to produce alkaloids has been studied in 13 strains belonging to ten species of the genus Penicillium. Most of these strains produce identical ranges of alkaloids when grown on wheat grain and synthetic Abe's medium. These are roquefortine, 3,12-dihydroroquefortine, and glandicolines A and B in strain P. chrysogenum VKM F-1987; fumigaclavines A and B, festuclavine, and pyroclavine in P. commune VKM F-308, F-3491, and KBP4; agroclavine 1 and epoxyagroclavine 1 in P. fellutanum VKM F-1073; fellutanine A in P. fellutanum F-3020; roquefortine, 3,12-dihydroroquefortine, meleagrin, and glandicolines A and B in P. glandicola VKM F-743; aurantioclavine in P. nalgiovense VKM F-229; isofumigaclavines A and B, festuclavine, roquefortine, and 3,12-dihydroroquefortine in P. roquefortii VKM F-2389; roquefortine, 3,12-dihydroroquefortine, and meleagrin in P. vitale VKM F-3624; roquefortine and oxaline in P. vulpinum VKM F-256; and -cyclopiazonic acid and rugulovasine B in P. viridicatum C-47. No alkaloids were found in P. rugulosum VKM F-352 grown on wheat grain. A simple method is proposed for isolating alkaloids from affected grain.     

Production of mycophenolic acid by fungi of the genus Penicillium link

Out of 36 strains of fungi of the genus Penicillium, some of which were isolated from ancient permafrost soils, 14 strains synthesized mycophenolic acid (MPA). Maximal (over 500 mg/l) accumulation of MPA in culture liquid was observed in P. brevicompactum strains (VKM F-457, VKM F-477, and VKM F-1150). This was the first study to detect MPA in representatives of the species P. rugulosum; in three strains of this species (VKM FW-665, VKM FW-717, and VKM FW-733), the level of MPA accumulation exceeded 300 mg/l. The time course of the synthesis of MPA by the P. rugulosum strain VKM FW-733 was studied. It was shown that the synthesis of this metabolite was dramatically intensified at the stationary growth phase (ten days).     

The Alkaloids of Penicillium aurantiogriseum Dierckx (1901) var. aurantiogriseum VKM F-1298

The fungus Penicillium aurantiogriseum var. aurantiogriseum VKM F-1298 produces two benzodiazepine alkaloids (anacine and aurantine) and one diketopiperazine alkaloid (aurantiamine). When cultured in a submerged mode in Abe medium, the alkaloids are mostly secreted into the medium. The dynamics of aurantine and aurantiamine accumulation in the medium is characterized by the presence of a relatively sharp maximum in the idiophase, whereas the accumulation of anacine in the medium is characterized by an extended plateau and occurs concurrently with fungal growth.     

Effect of mutation on synthesis of alkaloid byPenicillium roquefortii VKM F-141 andP. fellutanum VKM F-1073

Mutant strains ofPenicillium roquefortii VKM F-141 andP. fellutanum VKM F-1073 were obtained by mutagenesis induced by ultraviolet irradiation,N-methyl-N-nitronitrosoguanidine, and bromouracil. By the rates of alkaloid production, the mutant strains can be divided into three groups: (1) unable to synthesize alkaloids; (2) with a high rate of biosynthesis; (3) with changed alkaloid composition. Compounds not characteristic of wild-type cultures were found in alkaloid fractions of some mutant strains.     

Effect of the mutation process on formation of alkaloids in Penicillium roquefortii BKM F-141 and P. fellutanum BKM F-1073

Mutant strains of Penicillium roquefortii VKM F-141 and P. Fellutanum VKM F-1073 were obtained by mutagenesis induced by ultraviolet irradiation, N-methyl-N-nitronitrosoguanidine and bromouracil. By the rates of alkaloid production, the mutant strains can be divided into three groups: 1) unable to synthesize alkaloids; 2) with a high rate of biosynthesis; 3) with changed alkaloid composition. Compounds not characteristic of wild-type cultures were found in alkaloid fractions of some mutant strains.     

Production of mycophenolic acid by fungi of the genus <Emphasis Type="Italic">Penicillium</Emphasis> link

Out of 36 strains of fungi of the genus Penicillium, some of which were isolated from ancient permafrost, 14 strains synthesized mycophenolic acid (MPA). Maximal (over 500 mg/l) accumulation of MPA in culture liquid was observed in P. brevicompactum strains (VKM F-457, VKM F-477, and VKM F-1150). This was the first study to detect MPA in representatives of the species P. rugulosum; in three strains of this species (VKM FW-665, VKM FW-717, and VKM FW-733), the level of MPA accumulation exceeded 300 mg/l. The time course of the synthesis of MPA by P. rugulosum strain VKM FW-733 was studied. It was shown that the synthesis of this metabolite was dramatically intensified during the stationary growth phase (ten days).Translated from Prikladnaya Biokhimiya i Mikrobiologiya, Vol. 41, No. 1, 2005, pp. 95–98.Original Russian Text Copyright © 2005 by Vinokurova, Ivanushkina, Kochkina, Arinbasarov, Ozerskaya.     

Taxonomic position and nitrogen-containing secondary metabolites of the fungusPenicillium vitale pidoplichko et bilai apud bilai

The type strainPenicillium vitale Pidoplichko et Bilai apud Bilai 1961 VKM F-3624 was found to considerably differ from a sibling speciesP. janthinellium (syn.P. simplicissimum) in some physiological and morphological features (growth rates at different temperatures, the size of philiades, and the shape of conidia), as well as in the pattern of the nitrogen-containing secondary metabolites produced (roquefortine, 3,12-dihydroroquefortine, meleagrin, aurantioclavine, indole-3-acetic acid, andN-acetyltryptamine). The data obtained suggest thatP. vitale represents an independent species.     

Penicamedine A,a Highly Oxygenated Hexacyclic Indole Alkaloid from Penicillium camemberti

A highly oxygenated hexacyclic indole alkaloid, penicamedine A ( 1 ), bearing a rare furan ring, was isolated from the culture broth of Penicillium camemberti, together with two known analogs, iso‐α‐cyclopiazonic acid ( 2 ) and cyclopiazonic acid ( 3 ). The structure of 1 was elucidated by comprehensive spectroscopic analyses including NMR and HR‐ESI‐MS. Its absolute configuration was further confirmed unambiguously by single‐crystal X‐ray diffraction analysis. Compound 1 was evaluated for anti‐HIV activity with p24 assays and tested for cytotoxic activities against five human cancer cell lines, including HL‐60, SMMC‐7721, A‐549, MCF‐7, SW480, and the immortalized non‐cancerous human pulmonary epithelial cell line BEAS‐2B by MTS method.     

Germination of spores of mycelial fungi in relation to exogenous dormancy

Comparative analysis of germination of asexual sporulation spores (conidia and sporangiospores) and of specific features of dormancy release was carried out for ascomycete mycelial fungi Aspergillus tamarii VKM F-64 and A. sydowii VKM F-441, as well as for zygomycete fungi Cunninghamella echinulata VKM F-663 and Umbelopsis ramanniana VKM F-582. The spores of these strains were shown to be in a state of exogenous dormancy and differed in lag phase duration and germination rate, which depended on the presence of nutrients in the medium. Only the strain C. echinulata VKM F-663 exhibited 100% spore germination, with the germination rate and lag phase duration not depending on the composition of the medium. While in A. tamarii strain VKM F-64, the total number of spores germinating on rich and poor media was also almost the same, in the absence of nutrients lag phase duration increased and the germination rate decreased. For strains U. ramanniana VKM F-582 and A. sydowii VKM F-441, the degree of spore germination in the absence of nutrients in the medium was considerably lower than on the rich medium, while the lag phase was longer. These data indicate that the spores of C. echinulata VKM F-663 are in the state of exogenous dormancy, which does not require for release any compounds except water. The spores of U. ramanniana strain VKM F-582 and of the Aspergillus strains exhibited another variant of exogenous dormancy, which required for release, apart from water, also the sources of carbon and nitrogen. Thus, the character of dormancy release may differ even within a single genus (Aspergillus).     

Penicillium aurantiogriseum Dierckx 1901: Producer of Diketopiperazine Alkaloids (Roquefortine and 3,12-Dihydroroquefortine), Isolated from Permafrost

Secondary metabolites of three strains of Penicillium aurantiogriseumisolated from permafrost sediments were identified. It was found that these fungi synthesized the diketopiperazine alkaloids roquefortine and 3,12-dihydroroquefortine. The strain VKM FW-766 synthesized alkaloids in the course of certain growth-related processes. When the strain was grown on a mineral medium, the time courses of the roquefortine and 3,12-dihydroroquefortine concentrations were characterized by biphasic curves.     

Effect of microelements on the biosynthesis of secondary metabolites by the fungusPenicillium citrinum thom VKM F-1079

Penicillium citrinum VKM F-1079 was found to produce clavine ergot alkaloids and citrinin, a secondaryO-heterocyclic metabolite. Citrinin was produced in the idiophase, whereas the production of ergot alkaloids paralleled fungal growth. The addition of manganese ions to the growth medium stimulated the biosynthesis of both citrinin and ergot alkaloids. Zinc ions stimulated only citrinin synthesis. The presence of these microelements in the growth medium influenced the proportion between the ergot alkaloids synthesized. Copper, manganese, and iron ions slightly affected fungal growth and alkaloid production. The effect of microelements on the main kinetic parameters of growth and alkaloid production was studied.     

The alkaloids of Penicillium aurantiogriseum Dierckx (1901) var. aurantiogriseum VKM F-1298

The fungus Penicillium aurantiogriseum var. aurantiogriseum VKM F-1298 produces two benzodiazepine alkaloids (anacine and aurantine) and one diketopiperazine alkaloid (aurantiamine). When cultured in a submerged mode in Abe medium, the alkaloids are mostly secreted into the medium. The dynamics of aurantine and aurantiamine accumulation in the medium is characterized by the presence of a relatively sharp maximum in the idiophase, whereas the accumulation of anacine in the medium is characterized by an extended plateau and occurs concurrently with fungal growth.     

Carbohydrate-containing cell wall polymers of some strains of the <Emphasis Type="Italic">Bacillus subtilis</Emphasis> group

A comparative study of the structures of carbohydrate-containing cell wall polymers isolated from the strains of the Bacillus subtilis group was performed by means of chemical and NMR spectroscopic meth ods. Polymers of different structure were revealed, namely, 1,3-poly(glycerol phosphates) with β-glucopyranose in Bacillus subtilis strains VKM B-520, VKM B-723, and VKM B-763 (= VKM B-911); 1,5-poly(ribitol phosphate) with α-glucopyranose in B. subtilis strains VKM B-722 and VKM B-922 (the structure is reported for the first time); and simultaneously two polymers in B. subtilis VKM B-761, 1,5-poly(ribitol phosphate) with β-glucopyranose and the disaccharide 1-phosphate polymer with the following repeating unit: -6)-α-D-Galp-(1-P-4)-gB-D-GlcpNAc-(1-, in which the hydroxyls at C3 and C6 of glucosamine residues are partially O-acetylated (the structure is reported for the first time). Heterogeneity of the B. subtilis group is con firmed by variations in the structure and composition of the cell wall polymers. The cell surface polymers are useful for discrimination of closely related bacilli strains and are cell wall marker components that may be an indispensable element of the Bacillus subtilis group taxonomy along with the genomosystematic methods.     

Taxonomic position and nitrogen-containing secondary metabolites of the fungus Penicillium vitale Pidoplichko Et Bilai Apud Bilai

The type strain Penicillium vitale Pidoplichko et Bilai apud Bilai 1961 VKM F-3624 was found to considerably differ from a sibling species P. janthinellium (syn. P. simplicissimum) in some physiological and morphological features (growth rates at different temperatures, the size of philiades, and the shape of conidia), as well as in the pattern of the nitrogen-containing secondary metabolites produced (roquefortine, 3,12-dihydroroquefortine, meleagrin, aurantioclavine, indole-3-acetic acid, and N-acetyltryptamine). The data obtained suggest that P. vitale represent an independent species.     

Five New Triene Derivatives from the Fungus Penicillium herquei JX4

Five undescribed triene derivatives, pinophols B–F ( 2 – 6 ), together with one known compound, pinophol A ( 1 ), were obtained from the mangrove endophytic fungus Penicillium herquei JX4. The structures of compounds 1 – 6 were elucidated using IR, HR-ESI-MS, and NMR methods. The absolute configurations of compounds 1 – 6 were confirmed by comparing their experimental or calculated ECD spectra. Pinophols C and D ( 3 and 4 ) showed inhibitory activities against LPS-induced NO production.     

Resistance of Penicillium piceum F-648 to Hydrogen Peroxide under Short-Term and Prolonged Oxidative Stress

Resistance of Penicillium piceumF-648 to hydrogen peroxide under short-term and prolonged oxidative stress was studied. An increase in the activity of intracellular catalase in fungal cells after short-term exposure to hydrogen peroxide was shown. Activation of fungal cells induced by H₂O₂ depends on the H₂O₂ concentration, time of exposure, and growth phase of the fungus. Variants of P. piceum F-648 that produced two forms of extracellular catalase with different catalytic properties were obtained due to prolonged adaptation to H₂O₂. Catalase with low affinity for substrate was produced predominantly by the parent culture and variant 3; however, a high substrate affinity of catalase was observed in variant 5. Variant 5 of P. piceum F-648 displayed a high catalytic activity and operational stability of catalase in the presence of phosphate ions and a concentration of substrate less than 30 mM at pH more than 7.