Modularity of RiPP Enzymes Enables Designed Synthesis of Decorated Peptides.

ABSTRACT: Macrocyclases and other posttranslational enzymes afford derived peptides with improved properties for pharmaceutical and biotechnological applications. Here, we asked whether multiple posttranslational modifications could be simultaneously controlled and matched to rationally generate new peptide derivatives. We reconstituted the cyanobactin peptide natural products in vitro with up to five different posttranslational enzymes in a single tube. By manipulating the order of addition and identity of enzymes and exploiting their broad-substrate tolerance, we engineered the production of highly unnatural derivatives, including an N-C peptide macrocycle of 22 amino acids in length. In addition to engineering, this work better defines the macrocyclization mechanism, provides the first biochemica

SUBMITTER: Sardar D 

PROVIDER: S-EPMC4522240 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature