Structure-based engineering of substrate specificity for pinoresinol-lariciresinol reductases

Abstract Pinoresinol–lariciresinol reductases (PLRs) are enzymes involved in the lignan biosynthesis after initial dimerization of two monolignols, and this represents entry point for synthesis 8-8? lignans contributes greatly to their structural diversity. Of particular interest has been determination how differing substrate specificities achieved with these enzymes. Here, we present crystal structures Ii PLR1 from Isatis indigotica pinoresinol (PrRs) At PrR1 PrR2 Arabidopsis thaliana , apo, substrate-bound product-bound states. Each structure contains a head-to-tail homodimer, catalytic pocket comprises elements both monomers. ?4 loop covers top pocket, residue 98 governs specificity. The can be switched via structure-guided mutagenesis. Our study provides insight into molecular mechanism underlying specificity PLRs/PrRs suggests an efficient strategy large-scale commercial production pharmaceutically valuable compound lariciresinol.