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Microbiological Aspects in the Hydroxylation of Estrogens by Fusarium moniliforme

机译:镰刀菌镰刀菌对雌激素进行羟基化的微生物学方面

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A strain of Fusarium moniliforme (IH4), isolated from soil, showed outstanding enzymatic abilities to hydroxylate a number of estrogens. Estrone and estradiol were transformed into the 15α-hydroxy derivatives, and estradiol 3-methyl ether was transformed into the corresponding 6β-hydroxy derivative. Δ6-Estrone was not hydroxylated. The accumulation of 15α-hydroxyestrone was influenced by the nutritional conditions of the fungus. Maximal yield was obtained when the organism grew in Czapek solution supplemented with yeast extract, although good conversion was also found in a peptone-corn molasses medium. Substitution of NO3-N in Czapek medium with NH4-N, lactalbumin hydrolysate, Casitone, or Casamino Acids resulted in limited hydroxylation of estrone. A remarkable strain specificity was demonstrated in this conversion. Of 13 strains of F. moniliforme and Gibberella fujikuroi under investigation, only 2 strains (IH4 and ATCC 9851) accumulated substantial amounts of the 15α-hydroxylated product. However, marked quantitative variations were observed which are attributable to a different ability of the organisms to degrade the steroid nucleus. Biochemical instabilities were also found through the appearance of spontaneous variants lacking steroid-hydroxylating activity. Replacement culture studies revealed that 15α-hydroxylation of estrone was dependent on the supply of external phosphate; exogenous nitrogen or energy sources were not required. Most of the enzymatic activity was confined to the mycelia. Microconidia showed a very limited hydroxylating activity, even in the presence of supplements or energy sources.
机译:从土壤中分离出的镰刀菌镰刀菌(IH4)菌株具有出色的酶促能力,可以羟化许多雌激素。将雌酮和雌二醇转化为15α-羟基衍生物,并将雌二醇3-甲基醚转化为相应的6β-羟基衍生物。 Δ6-雌激素未羟基化。 15α-羟基雌酮的积累受真菌营养条件的影响。当该生物体在添加酵母提取物的Czapek溶液中生长时,尽管在蛋白ept-玉米糖蜜培养基中也发现了良好的转化,但仍能获得最大的产量。在Czapek培养基中用NH4-N,乳清蛋白水解物,Casitone或Cas氨基酸取代NO3-N会导致雌酮的羟基化作用受限。在这种转化中证明了显着的菌株特异性。在所研究的13株念珠菌和富士赤霉菌菌株中,只有2株(IH4和ATCC 9851)积累了大量15α-羟基化产物。然而,观察到明显的定量变化,这归因于生物体降解类固醇核的不同能力。通过缺乏类固醇羟化活性的自发变体的出现也发现了生化不稳定性。替代培养研究表明,雌酮的15α-羟化反应取决于外部磷酸盐的供应。不需要外源氮或能源。大多数的酶促活性都局限于菌丝体。即使在存在补充剂或能源的情况下,微分生孢子也表现出非常有限的羟化活性。

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