Pyridoxal 5′-Phosphate (PLP)-Dependent β- and γ-Substitution Reactions Forming Nonproteinogenic Amino Acids in Natural Product Biosynthesis

Living organisms synthesize various nonproteinogenic amino acids (NPAAs) as the building blocks of natural products. These NPAAs are often biosynthesized by pyridoxal 5'-phosphate (PLP)-dependent enzymes, which catalyze β- or γ- substitutions. These enzymes contribute to the structural diversification of NPAAs by installing new functional groups to amino acid side chains. Recent developments in genome mining have led to the identification of various PLP-dependent enzymes catalyzing β- or γ- substitutions, which form NPAAs in secondary metabolism. This short review summarizes recently investigated PLP-enzymes catalyzing β- or γ-substitutions in the biosynthesis of NPAAs by covering the literature published from 2015 through 2024.