Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase

Abstract

Engineering efforts have focused on acyltransferase (AT) domains of modular polyketide synthases (PKSs) to site-selectively modify the resulting polyketides, but critical AT residues involved in substrate selection have not been fully elucidated. Here, the authors use molecular dynamics to pinpoint mutations that impact AT domain selectivity and exchange structural motifs to obtain chimeric PKS modules with expanded substrate specificity.