An imine reductase that captures reactive intermediates in the biosynthesis of the indolocarbazole reductasporine.

ABSTRACT: Imine reductases (IREDs) and reductive aminases have been used in the synthesis of chiral amine products for drug manufacturing; however, little is known about their biological contexts. Here we employ structural studies and site-directed mutagenesis to interrogate the mechanism of the IRED RedE from the biosynthetic pathway to the indolocarbazole natural product reductasporine. Cocrystal structures with the substrate-mimic arcyriaflavin A reveal an extended active site cleft capable of binding two indolocarbazole molecules. Site-directed mutagenesis of a conserved aspartate in the primary binding site reveals a new role for this residue in anchoring the substrate above the NADPH cofactor. Variants targeting the secondary binding site greatly reduce catalytic efficiency, while accumulating

SUBMITTER: Daniel-Ivad P 

PROVIDER: S-EPMC10851217 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature