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Dive into the research topics where Marija Žakelj-Mavrič is active.

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Featured researches published by Marija Žakelj-Mavrič.


Biochemical Journal | 1999

A novel 17beta-hydroxysteroid dehydrogenase in the fungus Cochliobolus lunatus: new insights into the evolution of steroid-hormone signalling.

Tea Lanišnik Rižner; Gabriele Moeller; Hubert Thole; Marija Žakelj-Mavrič; Jerzy Adamski

17beta-Hydroxysteroid dehydrogenase (17beta-HSD) from the filamentous fungus Cochliobolus lunatus (17beta-HSDcl) catalyses the reduction of steroids and of several o- and p-quinones. After purification of the enzyme, its partial amino acid sequence was determined. A PCR fragment amplified with primers derived from peptide sequences was generated for screening the Coch. lunatus cDNA library. Three independent full-length cDNA clones were isolated and sequenced, revealing an 810-bp open reading frame encoding a 270-amino-acid protein. After expression in Escherichia coli and purification to homogeneity, the enzyme was found to be active towards androstenedione and menadione, and was able to form dimers of Mr 60000. The amino acid sequence of the novel 17beta-HSD demonstrated high homology with fungal carbonyl reductases, such as versicolorin reductase from Emericella nidulans (Aspergillus nidulans; VerA) and Asp. parasiticus (Ver1), polyhydroxynaphthalene reductase from Magnaporthe grisea, the product of the Brn1 gene from Coch. heterostrophus and a reductase from Colletotrichum lagenarium, which are all members of the short-chain dehydrogenase/reductase superfamily. 17beta-HSDcl is the first discovered fungal 17beta-hydroxysteroid dehydrogenase belonging to this family. The primary structure of this enzyme may therefore help to elucidate the evolutionary history of steroid dehydrogenases.


Journal of Steroid Biochemistry | 1987

Hydroxylation of steroids with 11α-hydroxylase of Rhizopus nigricans

Marija Žakelj-Mavrič; Igor Belič

Abstract Three groups of 3-keto-4-ene steroids with different side chains were used as substrates for the induced 11α -hydroxylase of Rhizopus nigricans . The highest total bioconversion as well as the highest yield of 11α-hydroxylated product is found using progesterone as substrate. By changing the polarity of the side chain, much higher yields of 6β- and 7β-hydroxylated products relative to 11α-hydroxylated product are obtained. Our results thus provide evidence for the importance of the side chain in steroid-enzyme interactions.


Comparative Biochemistry and Physiology B | 1995

Steroid hormone signalling system and fungi

Marija Žakelj-Mavrič; Tatjana Kastelic-Suhadolc; Ana Plemenitaš; Tea Lanišnik Rižner; Igor Belič

Three components of the steroid hormone signalling system, 17 beta-hydroxysteroid dehydrogenase, androgen binding proteins and steroid hormone signalling molecule testosterone were determined in the filamentous fungus Cochliobolus lunatus for the first time in a fungus. Their possible role in C. lunatus is discussed in comparison with their role in mammalian steroid hormone signalling system. The results are in accordance with the hypothesis, that the elements of primordial signal transduction system should exist in present day eukaryotic microorganisms.


Comparative Biochemistry and Physiology B | 2000

Characterization of fungal 17β-hydroxysteroid dehydrogenases

Tea Lanišnik Rižner; Marija Žakelj-Mavrič

Abstract To promote understanding of the evolution of the steroid hormone signalling and hydroxysteroid dehydrogenases (HSDs), comparative characterization of fungal 17β-HSDs was performed. Constitutive 17β-HSD activity was determined in cytosols of the fungi: Cochliobolus lunatus , Pleospora herbarum, Fusarium lini, Trichoderma viride, Mucor spinosus, Rhizopus nigricans and Pleurotus ostreatus . The reaction equilibrium in all species except P. ostreatus was shifted towards reduction. The preferential coenzyme for reduction of androstenedione was NADPH, while for oxidation of testosterone, NAD + was preferred. The highest enzyme activities were found in the Ascomycete C. lunatus (152.4 nmol mg −1 h −1 ) and in the Basidiomycete P. ostreatus (69.1 nmol mg −1 h −1 ). No similarities on the protein and mRNA level between fungal 17β-HSDs and the purified enzyme from C. lunatus were observed. To investigate the nature of these enzymes, 17β-HSD was purified from P. ostreatus using ammonium sulphate precipitation, hydrophobic interaction chromatography, and affinity chromatography. The purified enzyme has an apparent molecular mass of ∼35 kDa and is probably a dimer as determined by gel filtration. Chemical modifications exposed Lys, His and Tyr as important for enzyme activity. Additionally, no similarities of C. lunatus and P. ostreatus enzymes were found to bacterial 3α,20β-HSD from Streptomyces hydrogenans , 3β,17β-HSD from Comamonas testosteroni and mammalian 17β-HSD types 1 and 4. The results thus suggest that there are most probably different enzymes responsible for 17β-HSD activity in filamentous fungi.


Chemico-Biological Interactions | 2009

Aspects of the steroid response in fungi.

Bronislava Črešnar; Marija Žakelj-Mavrič

The number of fungal infections is increasing due to higher numbers of immunocompromised patients. Unfortunately, drug resistance represents a major additional problem in clinical praxis. Therefore factors contributing to infection by opportunistic pathogens, and to their growth and drug resistance are of major importance. It has been known for some time that mammalian steroid hormones are toxic to fungi. In this paper the response of fungi to the presence of steroid hormones will be discussed at different levels. First, the effect of steroid hormones on fungal growth, morphology and virulence will be considered. Processes affecting steroid intracellular concentration will be discussed; steroid uptake and, even more, steroid extrusion are currently of special interest. The role of biotransformation in the detoxification of active steroids will be taken into consideration and phases of steroid metabolism in fungal cells will be compared to phases of classical xenobiotic metabolism. Steroid signaling in fungi is presently not yet clear. It results in a global response of fungi to steroid hormones. Some of the genes differentially expressed in fungi as the result of exposure to steroid hormones may contribute to fungal drug resistance.


Comparative Biochemistry and Physiology B | 1999

Steroidogenesis in the fungus Pleurotus ostreatus

Ana Plemenitaš; Tatjana Kastelic-Suhadolc; Dušan Žigon; Marija Žakelj-Mavrič

Abstract The steroid hormones testosterone, androstenedione, progesterone and their metabolic products testosterone acetate and testololactone were identified as endogenously synthesised molecules in the fungus Pleurotus ostreatus . We discuss the possible steroidogenic pathway in the fungus in view of the evolutionary origin of the steroid hormone signalling system.


Journal of Steroid Biochemistry | 1989

Hydroxylation of steroids with nonpolar side chains with 11α-hydroxylase of Rhizopus nigricans

Marija Žakelj-Mavrič; Tatjana Kastelic-Suhadolc; Hugo E. Gottlieb; Igor Belič

Abstract Steroids with nonpolar side chains with 2, 4 and 8 C atoms were used as substrates for the 11α-hydroxylase of Rhizopus nigricans. Their bioconversion was compared to that of progesterone, which was found to be far the best substrate giving the highest total bioconversion. 3-keto-4-ene steroids with nonpolar side chains were converted to their hydroxylated products in a small yield or not at all. The absence of an oxygen function in the side chain did not affect the regio-specificity of the hydroxylation, but resulted in a much lower total bioconversion. The strong effect of the oxygen function and of the length of the side chain on hydroxylation with the 11α-hydroxylase of Rhizopus nigricans was demonstrated.


Steroids | 2008

Aspects of the progesterone response in Hortaea werneckii : Steroid detoxification, protein induction and remodelling of the cell wall

Lidija Križančić Bombek; Ajda Lapornik; Marjeta Ukmar; Maja Matis; Bronislava Črešnar; Jasna Peter Katalinić; Marija Žakelj-Mavrič

Progesterone in sublethal concentrations temporarily inhibits growth of Hortaea werneckii. This study investigates some of the compensatory mechanisms which are activated in the presence of progesterone and are most probably contributing to escape from growth inhibition. These mechanisms lead on the one hand to progesterone biotransformation/detoxification but, on the other, are suggested to increase the resistance of H. werneckii to the steroid. Biotransformation can detoxify progesterone efficiently in the early logarithmic phase, with mostly inducible steroid transforming enzymes, while progesterone biotransformation/detoxification in the late logarithmic and stationary phases of growth is not very efficient. The relative contribution of constitutive steroid transforming enzymes to progesterone biotransformation is increased in these latter phases of growth. In the presence of progesterone, activation of the cell wall integrity pathway is suggested by the overexpression of Pck2 which was detected in the stationary as well as the logarithmic phase of growth of the yeast. Progesterone treated H. werneckii cells were found to be more resistant to cell lysis than mock treated cells, indicating for the first time changes in the yeast cell wall as a result of treatment with progesterone.


Chemico-Biological Interactions | 2013

Steroid toxicity and detoxification in ascomycetous fungi

Damjana Cvelbar; Vanja Žist; Katja Kobal; Dušan Žigon; Marija Žakelj-Mavrič

In the last couple of decades fungal infections have become a significant clinical problem. A major interest into fungal steroid action has been provoked since research has proven that steroid hormones are toxic to fungi and affect the host/fungus relationship. Steroid hormones were found to differ in their antifungal activity in ascomycetous fungi Hortaea werneckii, Saccharomyces cerevisiae and Aspergillus oryzae. Dehydroepiandrosterone was shown to be the strongest inhibitor of growth in all three varieties of fungi followed by androstenedione and testosterone. For their protection, fungi use several mechanisms to lower the toxic effects of steroids. The efficiency of biotransformation in detoxification depended on the microorganism and steroid substrate used. Biotransformation was a relatively slow process as it also depended on the growth phase of the fungus. In addition to biotransformation, steroid extrusion out of the cells contributed to the lowering of the active intracellular steroid concentration. Plasma membrane Pdr5 transporter was found to be the most effective, followed by Snq2 transporter and vacuolar transporters Ybt1 and Ycf1. Proteins Aus1 and Dan1 were not found to be involved in steroid import. The research of possible targets of steroid hormone action in fungi suggests that steroid hormones inhibit ergosterol biosynthesis in S. cerevisiae and H. werneckii. Results of this inhibition caused changes in the sterol content of the cellular membrane. The presence of steroid hormones most probably causes the degradation of the Tat2 permease and impairment of tryptophan import.


Advances in Experimental Medicine and Biology | 1996

Carbonyl Reducing 17β-Hydroxysteroid Dehydrogenase from the Filamentous Fungus Cochliobolus lunatus

Tea Lanišnik Rižner; Zorko Matjaž; Jasna Peter-Katalinić; Kerstin Strupat; Marija Žakelj-Mavrič

Hydroxysteroid dehydrogenases (HSDs) which catalyse reversible oxidoreduction of ketosteroids and their respective hydroxysteroids have often been found to have additional substrate specificities towards nonsteroidal ketones, aldehydes and quinones (Maser, 1995). In mammals, such pluripotent enzymes were found in peripheral (Boutin, 1986; Hara et al., 1986;Hara et al. 1986a; Sawada et al., 1988; Klein et al., 1992; Maser and Bannenberg, 1994; Deyashiki et al., 1994; Ohara et al., 1994; Maser, 1995; Oppermann et al., 1995) as well as steroidogenic tissues (Tanaka et al., 1992; Nakajin et al., 1994; Jarabak et al., 1996). They were supposed to be involved in the detoxification of xenobiotic carbonyl compounds in addition to their role in the metabolism of endogenous steroids, prostaglandins, and quinones (Maser and Bannenberg, 1994; Oppermann et al., 1995). In microorganisms it has been shown for some bacterial HSDs that they have the versatility to accept steroidal as well as non-steroidal substrates (Oppermann et al., 1993; Maser, 1995). On the other hand, pluripotency of fungal HSD has not been discovered. Recently, 17β-hydroxysteroid dehydrogenase (17β-HSD) from the fungus Cochliobolus lunatus was purified and some of its molecular and kinetic properties were characterized (Lanisnik Rižner et al., 1996). In the present paper we provide further characterization of this enzyme and also some data indicating that it is a fungal enzyme with carbonyl reductase activity.

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Igor Belič

University of Ljubljana

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Maja Matis

University of Münster

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Katja Kobal

University of Ljubljana

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