[Secondary Metabolites of Fungi of the Usti Section, Genus Aspergillus and Their Application in Chemosystematics].

Secondary metabolites of 22 fungal strains (genus Aspergillus, section Usti) isolated at diverse geographic regions, including the Arctic permafrost deposits, were studied. The studied strains were found to synthesize a variety of biologically active compounds, structurally identified as drimane sesqueterpenoids, isoquinoline alkaloids (TMC-120 A−C, derivative 1), meroterpenoids (austalides О and J), and anthraquinone pigments (averufin, versicolorin C). Desferritriacetylfusigen production by A. calidoustus isolates is reported for the first time. The individual spectra of secondary metabolites were used for reidentification of 17 strains, of which 15 were identified as A. calidoustus and two, as A. pseudodeflectus.

[Exometabolites of the Fungal Isolates (Genus Penicillium, Section Chrysogena) from Low-Temperature Ecotopes].

Exometabolites of 22 strains of the genus Penicillium, section Chrysogena isolated from low-temperature ecotopes of various geographical regions were analyzed. The ecotopes included permafrost deposits, frozen volcanic ash, a fossil horse, cryopeg, and water from an Antarctic lake. The studied strains were found to contain exometabolites belonging to the groups of penicillins (penicillin G), chrysogins (chrysogin, 3-acetylquinazolone-4, 2-pyruvoyl aminobenzamide, 2-hydroxypropionyl amunobenzamide, and questiomycin A), roquefortines (3,12-dihydroroquefortine, roquefortine, glandicolines A and B, and meleagrine), xanthocillins (xanthocillin X), and simple tryptophan derivatives (N-acetyltriptamine and indoleacetic acid). In five P. chrysogenum strains and three P. nalgiovense strains a correlation was found between exometabolite spectra and morphological characteristics of the cultures isolated from modern ecotopes. For other strains species identification was based on morphological features, due to the absence of biosynthesis of penicillin G, on of the major chemotaxonomic markers for these species.

[Biosynthesis of biologically active low-molecular weight compounds by fungi of the genus Penicillium (review)].

The recent data on exometabolite biosynthesis in fungi of the genus Penicillium is summarized. The study of creative species, as well as those isolated from extreme ecotopes, resulted in the identification of a number of novel, biologically active compounds. Alkaloid biosynthesis has been shown to begin on.the first day of fungus cultivation and to proceed throughout the cultivation period. Idiophase kinetics was observed for the biosynthesis of polyketide metabolites. The mechanisms of regulation of biosynthesis of promising bioactive compounds are discussed.

Exo-metabolites of mycelial fungi isolated in production premises of cheese-making and meat-processing plants.

Data were obtained on the species composition of mycelial fungi isolated from the air of workrooms and production premises in cheese-making and meat-processing plants. The strains studied were shown to be capable of producing various low molecular weight compounds. Many of them are mycotoxins such as α-cyclopiazonic acid (CPA), mycophenolic acid (MPA), citrinin, cladosporin, roquefortine and ergot alkaloids. The profiles of the secondary metabolites were used to elucidate the species' names of the isolated strains.

[Fungi of the genus Penicillium as producers of physiologically active compounds (review)].

Fungi of the genus Penicillium isolated from little studied habitats are able to synthesize both previously known and new physiologically active compounds with diverse structures. They include secondary metabolites of alkaloid nature, i.e., ergot alkaloids, diketopiperazines, quinolines, quinazolines, benzodiazepines, and polyketides. We discuss the use of profiles of secondary metabolites for taxonomy purposes. Studying the physicochemical characteristics of producers of biologically active compounds showed that the biosynthesis of alkaloids is initiated on the first days of cultivation and proceeds simultaneously with growth. The cyclic character of alkaloid accumulation was recorded related to the processes of alkaloid biosynthesis, excretion from cells, degradation in culture fluid, and consumption by cells. Synchronic variations in the concentrations of intracellular tryptophan and alkaloids are necessary for the regulation of the optimal quantity of tryptophan necessary for the culture.

[Biosynthesis of fumiquinazolines by the fungus Penicillium thymicola].

Biosynthesis of fumiquinazolines F and G (FQs), PC-2, and pigments by the fungus P. thymicola VKM FW-869 is directly dependent on the content of carbon substrate (mannitol) in the medium. Pigment production prevailed at all of the tested mannitol concentrations. The necessary conditions for predominant FQ biosynthesis by the fungus P. thymicola are carbon source (mannitol) limitation and presence of NaCl in the cultivation medium. NaCl has a regulatory effect on the formation of secondary metabolites by enhancing FQ biosynthesis and reducing pigment formation. The maximum values of FQ biosynthesis and inhibition of pigment production are obtained at a mannitol concentration of 20 g/l and 2.5% NaCl in the medium.

[Physiological and biochemical characteristics of fungi of the genus Penicillium as producers of ergot alkaloids and quinocitrinins].

Four cultures of fungi of the genus Penicillium belonging to Furcatum Pitt subgenus, such as P. citrinum Thom, 1910; P. corylophilum Dierckx, 1901; P. fellutanum Biourge, 1923; and P. waksmanii Zaleski, 1927, produced the ergot alkaloids, namely, agroclavine-I, and epoxyagroclavine-I; their N-N-dimers, such as dimer of epoxyagroclavine-I and the mixed dimer of epoxyagroclavine-I and agroclavine-I; and also quinoline metabolites, namely, quinocitrinin A and quinocitrinin B. Physiological and biochemical characteristics of the producers were studied. Optimal conditions for the biosynthesis of metabolome components were determined. Zinc additive to the medium stimulated the biosynthesis of the ergot alkaloids in all cases; citrinin production was increased only in P. citrinum, and that was suppressed in P. corylophinum, P. fellutanum, and P. waksmanii. This testifies that genes of the biosynthesis pathways are located in the different clusters of the producers.

[New producers of biologically active compounds--fungal strains of the genus Penicillium isolated from permafrost].

Screening of producers of secondary metabolites was carried out among 25 fungal strains of Penicillium genus isolated from permafrost in Arctic and Antarctic regions and Kamchatka. Nearly 50% of the investigated strains synthesize biologically active substances of alkaloid nature: ergot alkaloids, diketopiperazines, and quinoline derivatives. A large group of the identified metabolites belongs to mycotoxins. A strain of Penicillium waksmanii was found producing epoxiagroclavine-I and quinocitrinins. The main physiological and biochemical characteristics of this producer were investigated.

[The influence of medium composition on alkaloid biosynthesis by Penicillium citrinum].

The fungus P. citrinum produces secondary metabolites, clavine ergot alkaloids (EA), and quinoline alkaloids quinocitrinines (QA) in medium with various carbon and nitrogen sources and in the presence of iron, copper, and zinc additives. Mannitol and sucrose are most favorable for EA biosynthesis and mannitol is most favorable for QA. Maximum alkaloid production is observed on urea. Iron and copper additives in the medium containing zinc ions stimulated fungal growth but inhibited alkaloid biosynthesis. The production of these secondary metabolites does not depend on the physiological state of culture, probably due to the constitutive nature of the enzymes involved in biosynthesis of these substances.

[Clavine alkaloid biosynthesis by the fungus Penicillium palitans westling 1911 isolated from ancient permafrost deposits].

The relic strain of Penicillium palitans isolated from the ancient permafrost deposits produces clavine alkaloids such as festuclavine, fumigaclavine A, and fumigaclavine B. Alkaloid biosynthesis is concurrent with the growth. Tryptophan and zinc ion additives to the culture medium stimulate the synthesis of alkaloids.

[Growth and biosynthesis of rugulovasines in Penicillium variabile Sopp 1912].

Production of clavine alkaloids rugulovasines by P. variabile did not depend on the habitat of the producers. During submerged cultivation on a simple synthetic medium in early growth stages, microcyclic conidiation was observed in the tested fungi; its presence or absence, as well as the activity of the cultures as to biosynthesis of rugulovasines, depended on the composition of the culture medium. On a complex medium supplemented with peptone, conidiation occurred but was considerably suppressed. Conidia were completely absent in the medium supplemented with yeast extract. In both cases, no appreciable amounts of rugulovasines were detected.

[The effect of some amino acids on the growth and biosynthesis of ergot alkaloids and quinocitrinins in the fungus Penicillium citrinum Thom 1910].

The effect of some amino acids, added to the medium either during inoculation or in the stationary growth phase, on the growth and biosynthesis of ergot alkaloids and quinocitrinins in the fungus Penicillium citrinum VKM FW-800 has been studied. Exogenously added amino acids were mostly utilized in primary metabolism. When added during inoculation, tryptophan and leucine virtually did not influence fungal growth and synthesis of the alkaloids, whereas the addition of isoleucine enhanced the biomass accumulation. When added in the stationary growth phase, tryptophan stimulated the synthesis of both ergot alkaloids and quinocitrinins. Leucine added in the stationary growth phase did not influence the synthesis of ergot alkaloids but inhibited the synthesis of quinocitrinins. Isoleucine inhibited the synthesis of both ergot alkaloids and quinocitrinins irrespective of the time of its addition to the medium.

[The fungus Penicillium variabile sopp 1912 isolated from permafrost deposits as a producer of rugulovasines].

It has been established that relict fungi Penicillium variabile Sopp can synthesize clavine alkaloids, rugulovasines A and B, which are revealed in this species for the first time. Submerged cultivation of the strain-producer revealed several microcycles of conidia formation. The synthesis of alkaloids was also of a cyclic character. The synchronism beween the cycles of rugulovasine biosynthesis and conidia formation was revealed. Zinc ions stimulated fungal growth but had a negative effect on the biosynthesis of rugulovasines.

[Fungus Penicillium citrinum, isolated from permafrost sediments, as a producer of ergot alkaloids and new quinoline alkaloids quinocitrinines].

Quinocitrinines and ergot alkaloids are synthesized by the strain Penicillium citrinum VKM FW-800 as the culture grows. The major part of these secondary metabolites are secreted into the medium. In the phase of growth deceleration, these metabolites were partly absorbed by the producer cells. Zinc ions stimulated both the primary and secondary metabolic processes. Addition of this microelement into the culture medium stimulated biomass accumulation and the synthesis of clavine alkaloids and quinocitrinines.

[Penicillium expansum, a resident fungal strain of the orbital complex Mir, producing xanthocillin X and questiomycin A]. / Grib Penicillium expansum--shtamm-rezident orbital'nogo komplexa "MIR"--produtsent ksantotsillina X i kvestiomitsina A.

It was demonstrated that the fungus Penicillium expansum 2-7, a resident strain of the orbital complex Mir, which became dominating at the end of a long-term space flight, formed biologically active secondary metabolites (antibiotics). Using physicochemical methods, these metabolites were identified as xanthocyllin X and questiomycin A. Time courses of their biosyntheses during growth and development of the producer culture were studied. Addition of zinc to the culture medium affected both the growth of the culture and the biosyntheses of the antibiotics. The concentrations of zinc in the medium, optimum for xanthocyllin X and questiomycin A production, amount to 0.3 and 3.0 mg/l, respectively.

[Isolation of Penicillium DIERCKX 1901--a producer of diketopiperazine alkaloids rokefortin and 3,12-dihydrokefortin--from permafrost]. / Vydelennye iz vechnoi merzloty griby Penicillium aurantiogriseum DIERCKX 1901--produtsenty diketopiperazinovykh alkaloidov rokefortina i 3/12-digidrorokefortina.

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

[The fungus Penicillium citrinum Thom 1910 VKM FW-800 isolated from ancient permafrost sediments as a producer of the ergot alkaloids agroclavine-1 and epoxyagroclavine-1]. / Grib Penicillium citrinum Thom 1910 VKM FW-800, vydelennyi iz vechnomerzlotnykh drevnikh otlozhenii kak produtsent érgoalkaloidov agroklavina-I i époksiagroklavina-I.

The study of the secondary metabolites of the relict strain Penicillium citrinum VKM FW-800 isolated from ancient Arctic permafrost sediments showed that this fungus produces agroclavine-1 and epoxyagroclavine-1, which are rare ergot alkaloids with the 5R,10S configuration of the tetracyclic ergoline ring system. The production of the alkaloids by the fungus showed a biphasic behavior, being intense in the phase of active growth and slowing down in the adaptive lag phase and in the stationary growth phase. The addition of zinc ions to the incubation medium led to a fivefold increase in the yield of the alkaloids. The alkaloids-producing Penicillium fungi isolated from different regions exhibited the same tendencies of growth and alkaloid production.

[The biosynthesis of low-molecular-weight nitrogen-containing secondary metabolite-alkaloids by the resident strains of Penicillium chrysogenum and Penicillium expansum isolated on the board of the Mir space station ]. / Biosintez nizkomolekuliarnykh azotsoderzhashchikh vtorichnykh metabolitov-alkaloidov shtammami-rezidentami gribov vidov Penicillium chrysogenum i Penicillium expansum, vydelennykh na orbital'noi stantsii "Mir".

The analysis of the absorption spectra of the low-molecular-weight nitrogen-containing secondary metabolites--alkaloids--of 4 Penicillium chrysogenum strains and 6 Penicillium expansum strains isolated on board the Mir space station showed that all these strains synthesize metabolites of alkaloid origin (roquefortine, 3,12-dihydroroquefortine, meleagrin, viridicatin, viridicatol, isorugulosuvin, rugulosuvin B, N-acetyl-tryptamine, and a "yellow metabolite" containing the benzoquinone chromophore).