发现并表征了一种具有降蒈烯形成 Diels-Alderase 的萜类生物合成途径。
Discovery and characterization of a terpene biosynthetic pathway featuring a norbornene-forming Diels-Alderase.
机构信息
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
出版信息
Nat Commun. 2022 May 11;13(1):2568. doi: 10.1038/s41467-022-30288-6.
Pericyclases, enzymes that catalyze pericyclic reactions, form an expanding family of enzymes that have biocatalytic utility. Despite the increasing number of pericyclases discovered, the Diels-Alder cyclization between a cyclopentadiene and an olefinic dienophile to form norbornene, which is among the best-studied cycloadditions in synthetic chemistry, has surprisingly no enzymatic counterpart to date. Here we report the discovery of a pathway featuring a norbornene synthase SdnG for the biosynthesis of sordaricin-the terpene precursor of antifungal natural product sordarin. Full reconstitution of sordaricin biosynthesis reveals a concise oxidative strategy used by Nature to transform an entirely hydrocarbon precursor into the highly functionalized substrate of SdnG for intramolecular Diels-Alder cycloaddition. SdnG generates the norbornene core of sordaricin and accelerates this reaction to suppress host-mediated redox modifications of the activated dienophile. Findings from this work expand the scopes of pericyclase-catalyzed reactions and P450-mediated terpene maturation.
周环酶是催化周环反应的酶，形成了一个不断扩大的酶家族，具有生物催化的用途。尽管已经发现了越来越多的周环酶，但迄今为止，在合成化学中研究最多的环加成反应之一，即环戊二烯和烯烃双烯亲合物之间的 Diels-Alder 环化反应，仍然没有酶的对应物。在这里，我们报告了一种途径的发现，该途径具有 norbornene 合酶 SdnG，用于合成 sordaricin-抗真菌天然产物 sordarin 的萜烯前体。sordaricin 生物合成的完全重组揭示了自然界用于将完全烃前体转化为 SdnG 的高度官能化底物的简洁氧化策略，用于分子内 Diels-Alder 环加成。SdnG 生成 sordaricin 的 norbornene 核心，并加速该反应以抑制宿主介导的活化双烯亲合物的氧化还原修饰。这项工作的结果扩展了周环酶催化反应和 P450 介导的萜类成熟的范围。
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