Identification of Two Distinct Stereoselective Lysine 5-Hydroxylases by Genome Mining Based on Alazopeptin Biosynthetic Enzymes.

ABSTRACT: Enzymes that catalyze regioselective and stereoselective hydroxylation of amino acids are useful tools for the synthesis of pharmaceuticals. AzpK is an unprecedented lysine 5-hydroxylase that is involved in alazopeptin biosynthesis, although its enzymatic activity has not been confirmed in vitro. Here, we identified two α-ketoglutarate/Fe²⁺-dependent dioxygenases in Actinosynnema mirum and Pseudomonas psychrotolerans (Am_AzpK2 and Pp_AzpK2, respectively) as lysine 5-hydroxylases, using genome mining based on the alazopeptin biosynthetic gene cluster. Interestingly, Am_AzpK2 and Pp_AzpK2 synthesized different isomers, (2S,5S)- and (2S,5R)-5-hydroxylysine, respectively. We also identified two AzpJ homologs as the dehydrogenases that specifically recognize the hydroxy groups of (2S

SUBMITTER: Kawai S 

PROVIDER: S-EPMC11973848 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature