Cyclization of amino acids against the peptide "backbone" is often performed, resulting in oxazolines and thiazolines; these can be further oxidized or reduced.
Nonribosomal peptides are a very diverse family of natural products with an extremely broad range of biological activities and pharmacological properties.
To become functional, the 4'-phospho-pantetheine sidechain of acyl-CoA molecules has to be attached to the PCP-domain by 4'PP transferases (Priming) and the S-attached acyl group has to be removed by specialized associated thioesterases (TE-II) (Deblocking).
[10] 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[11] and NRPSpredictor2,[12] have been developed to predict substrate specificity from DNA or protein sequence data.
Although there is high degree of similarity between the Carrier (PCP/ACP) domains of both types of synthetases, the mechanism of condensation is different from a chemical standpoint: