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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
氧化碳脊柱在瑞希利生物合成中的重新排列
Olga Tsypik1, Roman Makitrynskyy1, Britta Frensch2
1Department of Pharmaceutical Biology and Biotechnology, Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Stefan-Meier-Straße 19, 79104 Freiburg, Germany.
这项研究揭示了Streptomyces bottropensis酶RslO5,RslO9和RslO8如何重新排列聚基前体. 这些氧化还原定制步骤产生复杂的分子,如rishirilides和lupinacidin A.
科学领域:
- 生物化学
- 自然产品生物合成
- 酵素学
背景情况:
- 由于定制酶,II型多基体具有显著的结构多样性.
- 之前的C-标记研究表明,Streptomyces bottropensis在rishirilide生物合成中进行了复杂的重组.
研究的目的:
- 确定里希里里德和卢皮纳西丁A形成中的关键生物合成中间体.
- 阐明涉及到rishirilides A,B,D和lupinacidin A生物合成的复杂的氧化还原调整步骤.
主要方法:
- 在Streptomyces bottropensis中进行基因删除实验.
- 单独的定制酶的体外酶学研究.
- 生物合成中间体的表征
主要成果:
- 这种依赖于黄素的RslO5可减少环开放的环氧中间体.
- 弗拉单氧酶RslO9通过贝耶-维利格氧化和阿尔多尔凝结进行氧化碳骨干重新排列.
- 减酶RslO8对于形成里希里利德A和B是必不可少的,而RslO9则产生里希里利德D和卢皮纳基丁A.
结论:
- 不寻常的氧化还原定制反应,包括贝耶-维利格氧化和阿尔多尔凝结,推动了多基的结构多样化.
- 鉴定到的酶和途径为复杂的芳香聚化物天然产品的生物合成提供了洞察力.
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