Microbial Baeyer-Villiger oxidation of 5伪-steroids using Beauveria bassiana. A stereochemical requirement for the 11伪-hydroxylation and the lactonization pathway
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- 作者：Alina 艢wizdor ; alina.swizdor@up.wroc.pl" class="auth_mail ; Anna Panek ; Natalia Milecka-Tronina
- 关键词：Steroidal lactone ; Androstanedione ; 3伪-Androstanediol ; 17尾-Hydroxysteroid dehydrogenase ; Fungal 1-dehydrogenase ; Beauveria bassiana
- 刊名：Steroids
- 出版年：April, 2014
- 年：2014
- 卷：82
- 期：Complete
- 页码：44-52
- 全文大小：645 K
文摘
Beauveria bassiana KCH 1065, as was recently demonstrated, is unusual amongst fungal biocatalysts in that it converts C19 3-oxo-4-ene and 3尾-hydroxy-5-ene as well as 3尾-hydroxy-5伪-saturated steroids to 11伪-hydroxy ring-D lactones. The Baeyer-Villiger monooxygenase (BVMO) of this strain is distinguished from other enzymes catalyzing BVO of steroidal ketones by the fact that it oxidizes solely substrates with 11伪-hydroxyl group. The current study using a series of 5伪-saturated steroids (androsterone, 3伪-androstanediol and androstanedione) has highlighted that a small change of the steroid structure can result in significant differences of the metabolic fate. It was found that the 3伪-stereochemistry of hydroxyl group restricted 鈥渘ormal鈥?binding orientation of the substrate within 11伪-hydroxylase and, as a result, androsterone and 3伪-androstanediol were converted into a mixture of 7尾-, 11伪- and 7伪-hydroxy derivatives. Hydroxylation of androstanedione occurred only at the 11伪-position, indicating that the 3-oxo group limits the alternative binding orientation of the substrate within the hydroxylase. Only androstanedione and 3伪-androstanediol were metabolized to hydroxylactones. The study uniquely demonstrated preference for oxidation of equatorial (11伪-, 7尾-) hydroxyketones by BVMO from B. bassiana. The time course experiments suggested that the activity of 17尾-HSD is a factor determining the amount of produced ring-D lactones. The obtained 11伪-hydroxylactones underwent further transformations (oxy-red reactions) at C-3. During conversion of androstanedione, a minor dehydrogenation pathway was observed with generation of 11伪,17尾-dihydroxy-5伪-androst-1-en-3-one. The introduction of C1C2 double bond has been recorded in B. bassiana for the first time.