Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis

Adenylate-forming enzymes represent one of the most important enzyme classes in biology, responsible for the activation of carboxylate substrates for biosynthetic modifications. The by-product 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 non-ribosomal 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, ...