A. G. Kozlovskii

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.

The Biosynthesis of Low-Molecular-Weight Nitrogen-Containing Secondary Metabolites—Alkaloids—by the Resident Strains of Penicillium chrysogenum and Penicillium expansum Isolated on Board the Mir Space Station

The analysis of the absorption spectra of the low-molecular-weight nitrogen-containing secondary metabolites—alkaloids—of four Penicillium chrysogenum strains and six P. 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 acetyltryptamine, and a “yellow metabolite” containing the benzoquinone chromophore).

[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].

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 alkaloid-producing Penicillium fungi isolated from different regions exhibited the same tendencies of growth and alkaloid production.

Mycotoxin production profiles of Penicillium vulpinum (Cooke & Massee) Seifert & Samson strains.

Mycotoxins produced by seven strains ofPenicillium vulpinum (formerlyPenicillium claviforme) isolated from different sources were studied. The strains were characterized by specific profiles of secondary metabolites and produced mycotoxins of different structural types. In addition to toxins already known for this fungal species (patulin, roquefortine, 3,12-dihydroroquefortine, oxalin, viridicatin, cyclopenin, and α-cyclopiazonic acid), the strains studied also produced indolyl-3-acetic acid, griseofulvin, meleagrin, and cyclopeptin.

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 of cyclic rugulovasine biosynthesis and conidia formation was revealed. Zinc ions stimulated fungal growth but had a negative effect on the biosynthesis of rugulovasines.

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.

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.

Secondary Metabolite Profiles of the Penicillium Fungi Isolated from the Arctic and Antarctic Permafrost as Elements of Polyphase Taxonomy

The secondary metabolite profiles of the fungi of the subgenus Penicillium of the genus Penicillium isolated from permafrost were studied. Most of the tested strains synthesized biologically active alkaloids and polyketides. A novel producer of fumiquinazolines F and G was found. Species names of the strains were defined more exactly on the basis of their secondary metabolite profiles and micro- and macromorphological characteristics.

On the Mechanisms of the Excretion and Uptake of the Alkaloid Aurantioclavine during the Growth of the Fungus Penicillium nalgiovense VKM F-229

The biphasic dynamics of the alkaloid aurantioclavine in the culture liquid of P. nalgiovense VKM F-229 is shown to be due to the diauxic growth of the fungus on two carbon sources, succinate and mannitol. In the phase of active growth on succinate, the fungus synthesizes aurantioclavine and excretes it into the medium in an energy-independent manner, as a result of which the concentration of the alkaloid in the culture liquid rises. During the phase of metabolic adaptation to the other carbon source, mannitol, the concentration of aurantioclavine in the culture liquid falls, probably due to the energy-dependent uptake of the alkaloid by fungal cells. The reversible excretion of aurantioclavine in P. nalgiovense indicates that this process is regulatory and depends on the growth parameters and the physiological state of the fungus.

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.