Title:Recent Advances in Adenylation Domain Enzymology in Nonribosomal Peptide Biosynthesis
Volume: 19
Issue: 13
Author(s): Fumihiro Ishikawa and Hideaki Kakeya
Affiliation:
Keywords:
Adenylation domain, chemical proteomics, nonribosomal peptide synthetase, peptide-based natural product, protein engineering,
reprogramming, protein–protein interaction, synthetic probe.
Abstract: Microorganisms produce a large number of peptide-based natural products that display
a broad range of biologically interesting properties, including antimicrobial, immunosuppressant,
and anticancer activities, as well as behaving as virulence factors and signaling molecules. These
peptide natural products are composed of proteinogenic amino acids, as well as a number of other
compound classes, including non-proteinogenic amino acids, aryl acids, fatty acids, hydroxyl
acids, heterocyclic rings, and sugars, which provide a complex level of chemical diversity. Many
of these natural products are biosynthesized by large, highly versatile multifunctional megasynthetases,
which are known as nonribosomal peptide synthetases (NRPSs). The adenylation (A) domains found in all NRPS modules are
essential catalytic components and function as gatekeepers to select the appropriate amino acid building blocks during nonribosomal peptide
(NRP) biosynthesis. The results of extensive periods of genetic, biochemical, and bioinformatic investigations have provided a detailed
understanding of the functional characteristics and molecular basis underpinning the A domain enzymology in NRP biosynthesis.
This review will therefore focus on the recent discoveries and breakthroughs in the structural elucidation, molecular mechanism, and
chemical biology underlying the A domains within NRPS enzymes.
