Adenylation domain is a core domain in nonribosomal peptide synthetases.

Adenylation domain transfers an acyl unit onto its cognate carrier protein.

Recognition mechanism of noncanonical acyl units in adenylation domains is discussed.

Transient interactions of adenylation domains with carrier proteins are described.

Structural analysis of the interrupted adenylation domains is described.

Adenylation (A) domains catalyze the biosynthetic incorporation of acyl building blocks into nonribosomal peptides and related natural products by selectively transferring acyl substrates onto cognate carrier proteins (CP). The use of noncanonical acyl units, such as nonproteinogenic amino acids and keto acids, by A domains expands the structural diversity of natural products. Furthermore, interrupted A domains, which have embedded auxiliary domains, are able to modify the incorporated acyl units. Structural information on A domains is important for rational protein engineering to generate unnatural compounds. In this review, we summarize recent advances in the structural analysis of A domains. First, we discuss the mechanisms by which A domains recognize noncanonical acyl units. We then focus on the interactions of A domains with CP domains and embedded auxiliary domains.

Biosynthesis

Natural product

Nonribosomal peptide synthetase

Protein–protein interaction

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