Profiling of Diverse Pyridoxal-5'-Phosphate Dependent Enzymes Reveals Promiscuous Aldolase Activity with (2-Azaaryl)methanamines.

ABSTRACT: The elaboration of amine substrates through C-C bond-forming reactions is important in the synthesis of bioactive small molecules. Pyridoxal-5'-phosphate (PLP)-dependent enzymes have emerged as valuable biocatalysts for this class of reactions, due to their high stereoselectivity and ability to forge new C-C bonds on unprotected α-amino acid substrates. However, the use of abiological primary amines as pronucleophiles with enzymes such as threonine aldolase has been unexplored, moderating the utility of a biocatalytic approach in the synthesis of diverse 1,2-amino alcohols. In this report, we disclose the discovery and engineering of a PLP-dependent aldolase that accepts (2-azaaryl)methanamines in an aldol-type transformation. The 1,2-amino alcohol products generated, which contain represe

SUBMITTER: Smith KL 

PROVIDER: S-EPMC12320778 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature