Cracking the Nonribosomal Code David F. Ackerley  Cell Chemical Biology  Volume 23, Issue 5, Pages 535-537 (May 2016) DOI: 10.1016/j.chembiol.2016.05.001 Copyright © 2016 Elsevier Ltd Terms and Conditions

Figure 1 NRPS Assembly Line Technology Schematic of a three-module NRPS assembly line comprised of an initiation module (blue), an elongation module (green), and a termination module (yellow). Additional elongation modules may also be present, with each one governing incorporation of a further residue into the peptide product. To post-translationally activate the assembly line, a 4′-phosphopantetheine “swinging arm” (purple) is affixed by a specialized phosphopantetheinyl transferase enzyme to the thiolation (T-) domain (sometimes referred to as a peptidyl carrier protein [PCP-] domain) within each module. The first catalytic domain to act within each module is the adenylation (A-) domain (1), which activates a specific monomer by adenylation and then tethers it to the free sulfhydryl of the 4′-phosphopantetheine swinging arm of the T-domain immediately downstream. In a synchronized manner, beginning with the first elongation module (2), the condensation (C-) domains condense the upstream donor substrate with the downstream acceptor substrate. This reaction breaks the upstream thioester bond, yielding a peptidyl intermediate attached to the T-domain of the downstream module. This peptidyl intermediate in turn serves as the donor substrate for the C-domain of the next module in the assembly line. In a sequential process (3), the growing peptide chain is passed from module to module. Following addition of a final monomer by the termination module, the peptide product is released by a thioesterase (TE-) domain. Note that optional tailoring domains, catalyzing activities such as epimerization or methylation of specific monomers, may also be present within individual modules. Cell Chemical Biology 2016 23, 535-537DOI: (10.1016/j.chembiol.2016.05.001) Copyright © 2016 Elsevier Ltd Terms and Conditions