l-amino acid ligase: A promising alternative for the biosynthesis of l-dipeptides

Given their special action mechanisms and structural simplicity, L-amino acid ligases (Lals) are considered to be desirable tools for the catalytic biosynthesis of dipeptides. Ywf E (BacD) was the first Lal identified and was shown to be involved in the biosynthesis of a potent antibacterial, bacilysin, since then, various novel Lals have been discovered. Each Lal has different substrate spectra and is capable of synthesizing different dipeptides. Owning to their great potentials for producing bioactive dipeptides of industrial importance, in this review, recent developments of Lals are discussed, including their structures, action mechanisms, applications and the advantages and disadvantages of different Lals. In addition, protein engineering of Lals to improve their substrate specificity and catalytic performance is also discussed.