Adenylate-forming enzymes represent one of the most important enzyme classes in biology, responsible for the activation of carboxylate substrates for biosynthetic modifications. The byproduct of the adenylate-forming enzyme acetyl-CoA synthetase, acetyl-CoA, is incorporated into virtually every primary and secondary metabolic pathway. Modification of acetyl-CoA by an array of other adenylate-forming enzymes produces complex classes of natural products including nonribosomal peptides, polyketides, phenylpropanoids, lipopeptides, and terpenes. Adenylation domains possess a variety of unique structural and functional features that provide for such diversification in their resulting metabolites. As the number of organisms with sequenced genomes increases, more adenylate-forming enzymes are being identified, each with roles in metabolite production that have yet to be characterized. In this Review, we explore the broad role of class I adenylate-forming enzymes in the context of natural product biosynthesis and how they contribute to primary and secondary metabolism by focusing on important work conducted in the field. We highlight features of subclasses from this family that facilitate the production of structurally diverse metabolites, including those from noncanonical adenylation domains, and additionally discuss when biological roles for these compounds are known.

中文翻译：

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研究I类腺苷酸形成酶在天然产物生物合成中的作用。

形成腺苷酸的酶代表生物学中最重要的酶类别之一，负责活化羧酸酯底物以进行生物合成修饰。腺苷酸形成酶乙酰辅酶A合成酶的副产物乙酰辅酶A实际上被掺入每个主要和次要代谢途径中。一系列其他腺苷酸形成酶对乙酰辅酶A的修饰会产生复杂类别的天然产物，包括非核糖体肽，聚酮化合物，苯基丙烷，脂肽和萜烯。腺苷酸化结构域具有多种独特的结构和功能特征，这些特征在其所得代谢产物中提供了这种多样化。随着具有测序基因组的生物数量的增加，正在鉴定更多的形成腺苷酸的酶，每种在代谢产物生产中的作用尚待鉴定。在本综述中，我们将重点研究在该领域进行的重要工作，探讨I类腺苷酸形成酶在天然产物生物合成中的广泛作用，以及它们如何促进一次和二次代谢。我们重点介绍了该家族亚类的特征，这些亚类可促进结构多样的代谢产物的生产，包括那些来自非规范腺苷酸化结构域的代谢产物，并进一步讨论了何时知道这些化合物的生物学作用。