Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition.
Involvement of Lipocalin-like CghA in Decalin-Forming Stereoselective Intramolecular [4+2] Cycloaddition.
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DOI：
10.1002/cbic.201500386
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发表时间：
2015-11-02
期刊：
影响因子：
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通讯作者：
Watanabe K
中科院分区：
文献类型：
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作者：
Sato M;Yagishita F;Mino T;Uchiyama N;Patel A;Chooi YH;Goda Y;Xu W;Noguchi H;Yamamoto T;Hotta K;Houk KN;Tang Y;Watanabe K
了解酶促Diels-Alder（DA）反应，可以形成复杂的天然产物支架是相当感兴趣的。Sch 210972 1是一种潜在的抗HIV真菌天然产物，含有十氢萘核，其被提议通过DA反应形成。我们确定了负责1的生物合成的基因簇，并异源重建构巢曲霉中的生物合成途径，以表征所涉及的酶。最值得注意的是，cghA的缺失导致立体选择性萘烷核心形成的损失，产生所提出的DA反应的内1和非对映体外加合物。与cghA互补恢复了1的唯一形成。建议DA反应的密度泛函理论计算提供了一个合理的解释所观察到的产品形成模式。基于我们的研究，我们提出，脂质运载蛋白样CghA是负责立体选择性的分子内[4+2]环加成，形成萘烷核心的1。
Understanding enzymatic Diels—Alder (DA) reactions that can form complex natural product scaffold is of considerable interest. Sch 210972 1, a potential anti-HIV fungal natural product, contains a decalin core that is proposed to form via a DA reaction. We identified the gene cluster responsible for the biosynthesis of 1 and heterologously reconstituted the biosynthetic pathway in Aspergillus nidulans to characterize the enzymes involved. Most notably, deletion of cghA resulted in a loss of stereoselective decalin core formation, yielding both an endo 1 and a diastereomeric exo adducts of the proposed DA reaction. Complementation with cghA restored the sole formation of 1. Density functional theory computation of the proposed DA reaction provided a plausible explanation of the observed pattern of product formation. Based on our study, we propose that lipocalin-like CghA is responsible for the stereoselective intramolecular [4+2] cycloaddition that forms the decalin core of 1.