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首页> 外文期刊>Biochemistry >Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile-Containing Natural Products
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Examining Reaction Specificity in PvcB, a Source of Diversity in Isonitrile-Containing Natural Products

机译：检查PvcB中的反应特异性，PvcB是含有异腈的天然产物的多样性来源

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摘要

Many bacteria produce isonitrile-containing natural products that are derived from aromatic amino acids. The synthetic clusters that control biosynthesis most commonly encode two enzymes, designated PvcA and PvcB, as well as additional enzymes that direct synthesis of the natural product. The PvcA enzyme installs the isonitrile moiety at the amino group of either tyrosine or tryptophan, as dictated by the particular pathway. The common pathway intermediate produced by PvcA is directed toward different ultimate products by PvcB, a member of the family of Fe2+, alpha-ketoglutarate-dependent oxygenases. To continue our investigation of the structural and functional properties of the isonitrile biosynthetic pathways, we present here a study of the PvcB homologues from three organisms. Two pathways, derived from Pseudomonas aeruginosa and Xenorhabdus nematophila, produce known products. A third PvcB homologue from Erwinia amylovora is part of an uncharacterized pathway. Our results demonstrate the diversity of reactions catalyzed. Although all PvcB enzymes catalyze the hydroxylation of the tyrosine isonitrile substrate, the elimination of the hydroxyl in Pseudomonas and Erwinia is driven by deprotonation at C alpha, resulting in the initial production of an unsaturated tyrosine isonitrile product that then cyclizes to a coumarin derivative. PvcB from Xenorhabdus, in contrast, catalyzes the same oxygenation, but loss of the hydroxyl group is accompanied by decarboxylation of the intermediate. Steady-state kinetic analysis of the three reactions and a docking model for the binding of the tyrosine isonitrile substrate in the PvcB active site highlight subtle differences between the PvcB homologues.
机译：许多细菌会产生含有异腈的天然产物，这些产物衍生自芳香族氨基酸。控制生物合成的合成簇通常编码两种酶，称为PvcA和PvcB，以及指导天然产物合成的其他酶。 PvcA酶根据特定途径将异腈部分安装在酪氨酸或色氨酸的氨基上。 PvcA产生的常见途径中间体是由PvcB（Fe2 +，α-酮戊二酸依赖性加氧酶）家族的成员针对不同的最终产物。为了继续我们对异腈生物合成途径的结构和功能特性的研究，我们在此介绍对三种生物的PvcB同源物的研究。源自铜绿假单胞菌和线虫Xenorhabdus nematophila的两条途径产生已知产物。来自解淀粉欧文氏菌（Erwinia amylovora）的第三个PvcB同源物是未知途径的一部分。我们的结果证明了所催化反应的多样性。尽管所有PvcB酶均催化酪氨酸异腈底物的羟基化反应，但假单胞菌和欧文氏菌中羟基的消除是由Cα处的去质子化驱动的，导致了不饱和酪氨酸异腈产物的初始生成，然后环化成香豆素衍生物。相比之下，来自Xenorhabdus的PvcB催化相同的氧化，但是羟基的损失伴随着中间体的脱羧。三个反应的稳态动力学分析和酪氨酸异腈底物在PvcB活性位点结合的对接模型突出了PvcB同源物之间的细微差异。

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