The role of cytochrome P45011α in detoxification of steroids in the filamentous fungus Rhizopus nigricans

Breskvar, Katja; Ferenčak, Zdenka; Hudnik-Plevnik, Tamara

doi:10.1016/0960-0760(94)00169-m

Cited by 39 publications

(28 citation statements)

References 6 publications

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“…Specifically, the filamentous fungi Rhizopus nigricans and Cochliobolus lunatus were shown to convert the steroid progesterone into the pharmaceutically important compound 11␣-hydroxyprogesterone [3,4]. Although the biological role of progesterone transformation in fungi is currently unknown, it has been suggested as a mechanism for enzymatic detoxification of a fungitoxic substrate [5]. This hypothesis is supported by several lines of evidence.…”

Section: Introductionsupporting

confidence: 59%

“…First, progesterone inhibits hyphal growth of R. nigricans and severely affects its morphology [6]. Second, the hydroxylated product is more water-soluble and therefore easily removed from mycelia surrounded by water [5]. Third, progesterone hydroxylase in R. nigricans is an inducible cytochrome P450-containing enzyme system which is involved in the transformation of xenobiotics [7].…”

Section: Introductionmentioning

confidence: 99%

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Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Poli¹,

Pietro²,

Žigon³

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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a b s t r a c tFungi present the ability to hydroxylate steroids. In some filamentous fungi, progesterone induces an enzyme system which converts the compound into a less toxic hydroxylated product. We investigated the progesterone response in the vascular wilt pathogen Fusarium oxysporum, using mass spectrometry and high performance liquid chromatography (HPLC). Progesterone was mainly transformed into 15␣-hydroxyprogesterone, which was found predominantly in the extracellular medium. The role of two conserved fungal signaling cascades in the induction of the progesterone-transforming enzyme system was studied, using knockout mutants lacking the mitogen-activated protein kinase Fmk1 or the heterotrimeric G-protein ␤ subunit Fgb1 functioning upstream of the cyclic adenosine monophosphate (cAMP) pathway. No steroid hydroxylation was induced in the fgb1 strain, suggesting a role for the G-protein ␤ subunit in progesterone signaling. Exogenous cAMP restored the induction of progesteronetransforming activity in the fgb1 strain, suggesting that steroid signaling in F. oxysporum is mediated by the cAMP-PKA pathway.

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Section: Introductionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Poli¹,

Pietro²,

Žigon³

et al. 2009

The Journal of Steroid Biochemistry and Molecular Biology

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“…process leading to progesterone being made less toxic, possibly by hydroxylation by induced enzymes [3].…”

Section: % Of [mentioning

confidence: 99%

“…In the search for an antagonist of membrane progesterone receptors we examined the competitive ability of Knaphtho£avone, previously shown to inhibit progesterone induced steroid-hydroxylase activity [3]. K-Naphtho£a-vone competed e⁄ciently for cytosolic but not for membrane-bound progesterone receptors (Fig.…”

Section: Progesterone Binding and Steroid Speci¢city Of Membrane Recementioning

confidence: 99%

“…In addition to mammalian pathogenic fungi, growth inhibition by mammalian steroids, especially progesterone and 21-hydroxyprogesterone, was observed also in the saprophytic fungus Rhizopus nigricans [3]. In response to progesterone action this fungus has evolved defense mechanisms including heat shock protein synthesis [4], sugar epimerase gene expression [5], and induction of progesterone hydroxylating enzyme(s) [6] which transform progesterone into less toxic and more easily removable hydroxy-products [3].…”

Section: Introductionmentioning

confidence: 99%

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Membrane-bound progesterone receptors coupled to G proteins in the fungus Rhizopus nigricans

Lenasi

2002

FEMS Microbiology Letters

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Steroid binding sites with high affinity for progesterone (K d = 40 þ 14 nM determined by binding, and K d = 71 þ 22 nM determined by displacement studies) and lower affinity for 21-hydroxyprogesterone and for testosterone, but no affinity for estradiol-17L, onapristone and K-naphthoflavone were detected in the enriched plasma membrane fraction of the fungus Rhizopus nigricans. The amount of steroid binding sites is in accordance with the value of B max = 744 þ 151 fmol (mg protein)31 . In the membrane fraction, progesterone induced about 30% activation of G proteins over basal level, as determined by GTPase activity (EC 50 = 32 þ 8 nM) and by the guanosine 5P-O-(3-thiotriphosphate) (GTPQS) binding rate (EC 50 = 61 þ 21 nM). The affinity of receptors for progesterone was substantially decreased in the presence of GTPQS and of cholera toxin. Our results suggest the existence of progesterone receptors in the membrane of Rhizopus nigricans and their coupling to G proteins. ß

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The response of filamentous fungus Rhizopus nigricans to flavonoids

Slana

Žigon

Makovec

et al. 2011

J. Basic Microbiol.

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The saprophytic fungus Rhizopus nigricans constitutes a serious problem when thriving on gathered crops. The identification of any compounds, especially natural ones, that inhibit fungal growth, may therefore be important. During its life cycle, Rhizopus nigricans encounters many compounds, among them the flavonoids, plant secondary metabolites that are involved in plant defense against pathogenic microorganisms. Although not being a plant pathogen, Rhizopus nigricans may interact with these compounds in the same way as plant pathogens--in response to the fungitoxic effect of flavonoids the fungi transform them into less toxic metabolites. We have studied the interaction of R. nigricans with some flavonoids. Inhibition of hyphal spreading (from 3% to 100%) was observed by 300 μM flavones, flavanones and isoflavones, irrespective of their basic structure, oxidized or reduced C-ring, and orientation of the B-ring. However, a hydrophobic A-ring was important for the toxicity. R. nigricans transformed some of the flavonoids into glucosylated products. Recognition of substrates for glucosylating enzyme(s) did not correlate with their fungitoxic effect but depended exclusively on the presence of a free -OH group in the flavonoid A-ring and of a hydrophobic B-ring. Although the fungus produced glucosyltransferase constitutively, an additional amount of the enzyme was induced by the substrate flavonoid. Moreover, effective detoxification was shown to require the presence of glucose.

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The role of cytochrome P45011α in detoxification of steroids in the filamentous fungus Rhizopus nigricans

Cited by 39 publications

References 6 publications

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Possible involvement of G-proteins and cAMP in the induction of progesterone hydroxylating enzyme system in the vascular wilt fungus Fusarium oxysporum

Membrane-bound progesterone receptors coupled to G proteins in the fungus Rhizopus nigricans

The response of filamentous fungus Rhizopus nigricans to flavonoids

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