text: Most domains have a very broad substrate specificity and usually only the A-domain determines which amino acid is incorporated in a module. Ten amino acids that control substrate specificity and can be considered the codons of nonribosomal peptide synthesis have been identified, and rational protein design has yielded methodologies to computationally switch the specificities of A-domains.  The condensation C-domain is also believed to have substrate specificity, especially if located behind an epimerase E-domain-containing module where it functions as a filter for the epimerized isomer. Computational methods, such as SANDPUMA and NRPSpredictor2, have been developed to predict substrate specificity from DNA or protein sequence data.