Engineered Biocatalytic Synthesis of β-N-Substituted-α-Amino Acids.

ABSTRACT: Non-canonical amino acids (ncAAs) are useful synthons for the development of new medicines, materials, and probes for bioactivity. Recently, enzyme engineering has been leveraged to produce a suite of highly active enzymes for the synthesis of β-substituted amino acids. However, there are few examples of biocatalytic N-substitution reactions to make α,β-diamino acids. In this study, we used directed evolution to engineer the β-subunit of tryptophan synthase, TrpB, for improved activity with diverse amine nucleophiles. Mechanistic analysis shows that high yields are hindered by product re-entry into the catalytic cycle and subsequent decomposition. Additional equivalents of l-serine can inhibit product reentry through kinetic competition, facilitating preparative scale synthesis. We show β-

SUBMITTER: Villalona J 

PROVIDER: S-EPMC10592029 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature