In detail, describe the process of non-ribosomal peptide synthesis as catalysed by non-ribosomal peptide synthetases, requisite enzyme post-translational modification via 4′-phosphopantetheinyl transferase, and outline selected examples of non-ribosomal peptide uses. Use diagrams where necessary. Non-ribosomal Peptide Synthesis and 4′-Phosphopantetheinyl Transferase-Mediated Post-Translational Modification

Non-ribosomal Peptide Synthesis and 4′-Phosphopantetheinyl Transferase-Mediated Post-Translational Modification

Non-ribosomal peptide synthesis (NRPS) is a process by which peptides are synthesized by the catalysis of enzymes known as non-ribosomal peptide synthetases (NRPSs). This process is distinct from the more traditional ribosomal peptide synthesis, which involves the translation of mRNA into amino acid chains via transfer RNAs. In NRPS, there are two main stages: 1) the assembly of the peptide by the NRPS and 2) the post-translational modification of the peptide by 4′-phosphopantetheine transferase (PPTase) (Bednarski et al., 2020). This article will outline the process of NRPS, the role of PPTase, and examples of the various uses of NRPS products. The NRPS is a complex multienzyme system that catalyzes the formation of peptides from activated monomers, known as aminoacyl adenylates (AAs). This is done by the sequential addition of AAs to a growing peptide chain, with each AA being selected by the NRPS based on the presence of specific substrates. This process is mediated by several domains in the NRPS, including adenylation (A), thiolation (T), condensation (C), and release (R) domains (Chu et al., 2020). Following the assembly of the peptide chain, the peptide is modified by the action of PPTase. This enzyme catalyzes the transfer of 4′-phosphopantetheine (4PP) to peptide thiols, which is necessary for the peptide to be active. NRPS products have a wide range of applications in biotechnology, medicine, and agriculture. Examples of NRPS-derived products include antibiotics such as vancomycin and. Cont…