Biosynthesis of natural products containing β-amino acids

We focus here on beta-amino acids as components of complex natural products because the presence of beta-amino acids produces structural diversity in natural products and provides characteristic architectures beyond those of ordinary alpha-L-amino acids, thus generating significant and unique biological functions in nature. In this review, we first survey the known bioactive beta-amino acid-containing natural products including nonribosomal peptides, macrolactam polyketides, and nucleoside-beta-amino acid hybrids. Next, the biosynthetic enzymes that form beta-amino acids from beta-amino acids and the de novo synthesis of beta-amino acids are summarized. Then, the mechanisms of beta-amino acid incorporation into natural products are reviewed. Because it is anticipated that the rational swapping of the beta-amino acid moieties with various side chains and stereochemistries by biosynthetic engineering should lead to the creation of novel architectures and bioactive compounds, the accumulation of knowledge regarding beta-amino acid-containing natural product biosynthetic machinery could have a significant impact in this field. In addition, genome mining of characteristic beta-amino acid biosynthetic genes and unique beta-amino acid incorporation machinery could lead to the discovery of new beta-amino acid-containing natural products.