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

ABSTRACT: Polyketides, one of the largest classes of natural products, are often clinically relevant. The ability to engineer polyketide biosynthesis to produce analogs is critically important. Acyltransferases (ATs) of modular polyketide synthases (PKSs) catalyze the installation of malonyl-CoA extenders into polyketide scaffolds. ATs have been targeted extensively to site-selectively introduce various extenders into polyketides. Yet, a complete inventory of AT residues responsible for substrate selection has not been established, limiting the scope of AT engineering. Here, molecular dynamics simulations are used to prioritize ~50 mutations within the active site of EryAT6 from erythromycin biosynthesis, leading to identification of two previously unexplored structural motifs. Exchanging both motif

SUBMITTER: Kalkreuter E 

PROVIDER: S-EPMC8044089 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature