Exploiting a C-N Bond Forming Cytochrome P450 Monooxygenase for C-S Bond Formation.,Angewandte Chemie International Edition

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Exploiting a C-N Bond Forming Cytochrome P450 Monooxygenase for C-S Bond Formation.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2019-12-30 , DOI: 10.1002/anie.201916269
Iori Morita ₁ , Takahiro Mori _{1,

2} , Takaaki Mitsuhashi ₁ , Shotaro Hoshino ₁ , Yoshimasa Taniguchi ₃ , Takashi Kikuchi ₄ , Kei Nagae ₅ , Norihiro Nasu ₆ , Makoto Fujita _{7,

8} , Tomohiko Ohwada ₁ , Ikuro Abe _{1,

2}

Affiliation

C-S bond formation reactions are widely distributed in the biosynthesis of biologically active molecules, and thus have received much attention over the past decades. Herein, we report intramolecular C-S bond formation by a P450 monooxygenase, TleB, which normally catalyzes a C-N bond formation in teleocidin biosynthesis. Based on the proposed reaction mechanism of TleB, a thiol-substituted substrate analogue was synthesized and tested in the enzyme reaction, which afforded the unprecedented sulfur-containing thio-indolactam V, in addition to an unusual indole-fused 6/5/8-tricyclic product whose structure was determined by the crystalline sponge method. Interestingly, conformational analysis revealed that the SOFA conformation is stable in thio-indolactam V, in sharp contrast to the major TWIST form in indolactam V, resulting in differences in their biological activities.

中文翻译：

利用CN键形成细胞色素P450单加氧酶进行CS键形成。

CS键形成反应广泛地分布在生物活性分子的生物合成中，因此在过去的几十年中受到了广泛的关注。在本文中，我们报道了通过P450单加氧酶TleB分子内CS键的形成，该酶通常会在Teleocidin生物合成中催化CN键的形成。根据拟议的TleB反应机理，合成并测试了巯基取代的底物类似物，并在酶反应中进行了测试，除具有不寻常的吲哚稠合的6/5 / 8-外，还提供了前所未有的含硫硫代吲哚内酰胺V。通过结晶海绵法确定其结构的三环产物。有趣的是，构象分析表明，SOFA构象在硫代吲哚内酰胺V中是稳定的，这与吲哚内酰胺V中的主要TWIST形式形成鲜明对比，

更新日期：2020-01-23

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