Directed Evolution Reveals the Functional Sequence Space of an Adenylation Domain Specificity Code.

ABSTRACT: Nonribosomal peptides are important natural products biosynthesized by nonribosomal peptide synthetases (NRPSs). Adenylation (A) domains of NRPSs are highly specific for the substrate they recognize. This recognition is determined by 10 residues in the substrate-binding pocket, termed the specificity code. This finding led to the proposal that nonribosomal peptides could be altered by specificity code swapping. Unfortunately, this approach has proven, with few exceptions, to be unproductive; changing the specificity code typically results in broadened specificity or poor function. To enhance our understanding of A domain substrate selectivity, we carried out a detailed analysis of the specificity code from the A domain of EntF, an NRPS involved in enterobactin biosynthesis in Escherichi

SUBMITTER: Throckmorton K 

PROVIDER: S-EPMC6800085 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature