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Side chain removal from corticosteroids by unspecific peroxygenase
Journal of Inorganic Biochemistry ( IF 3.8 ) Pub Date : 2018-03-26 , DOI: 10.1016/j.jinorgbio.2018.03.011
René Ullrich , Marzena Poraj-Kobielska , Steffi Scholze , Claire Halbout , Martin Sandvoss , Marek J. Pecyna , Katrin Scheibner , Martin Hofrichter

Two unspecific peroxygenases (UPO, EC 1.11.2.1) from the basidiomycetous fungi Marasmius rotula and Marasmius wettsteinii oxidized steroids with hydroxyacetyl and hydroxyl functionalities at C17 - such as cortisone, Reichstein's substance S and prednisone - via stepwise oxygenation and final fission of the side chain. The sequential oxidation started with the hydroxylation of the terminal carbon (C21) leading to a stable geminal alcohol (e.g. cortisone 21-gem-diol) and proceeded via a second oxygenation resulting in the corresponding α-ketocarboxylic acid (e.g. cortisone 21-oic acid). The latter decomposed under formation of adrenosterone (4-androstene-3,11,17-trione) as well as formic acid and carbonic acid (that is in equilibrium with carbon dioxide); fission products comprising two carbon atoms such as glycolic acid or glyoxylic acid were not detected. Protein models based on the crystal structure data of MroUPO (Marasmius rotula unspecific peroxygenase) revealed that the bulky cortisone molecule suitably fits into the enzyme's access channel, which enables the heme iron to come in close contact to the carbons (C21, C20) of the steroidal side chain. ICP-MS analysis of purified MroUPO confirmed the presence of magnesium supposedly stabilizing the porphyrin ring system.



中文翻译:

通过非特异性过氧化酶从皮质类固醇中去除侧链

担子菌真菌Roas Mariusius rotulaMarasmius wettsteinii的两种非特异性过氧合酶(UPO,EC 1.11.2.1)在C17处通过逐步氧化和侧链最终裂变,氧化了在C17具有羟基乙酰基和羟基官能团的类固醇,例如可的松,Reichstein物质S和泼尼松。 。顺序氧化始于末端碳(C21)的羟基化反应,从而产生稳定的宝石醇(例如可的松21-宝石)-二醇),并通过第二次氧化进行反应,得到相应的α-酮羧酸(例如,可的松21-油酸)。后者在形成肾上腺素(4-雄烯酮-3,11,17-三酮)以及甲酸和碳酸(与二氧化碳处于平衡状态)时分解;没有检测到包含两个碳原子的裂变产物,例如乙醇酸或乙醛酸。基于Mro UPO(Marasmius rotula非特异性过氧化酶)晶体结构数据的蛋白质模型显示,庞大的可的松分子适合进入酶的通道,这使血红素铁与Cro的碳(C21,C20)紧密接触。类固醇侧链。纯化Mro的ICP-MS分析UPO证实存在镁,据说可以稳定卟啉环系统。

更新日期:2018-03-26
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