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