Cyclosporin A (CsA)

CsA is an immunosuppressant drug widely used in organ transplantation to prevent rejection. It reduces the activity of the immune system by interfering with the activity and growth of T cells.Ciclosporin is synthesized by a nonribosomal peptide synthetase, ciclosporin synthetase. The enzyme contains an adenylation domain, a thiolation domain, a condensation domain, and an N-methyltransferase domain. The adenylation domain is responsible for substrate recognition and activation, whereas the thiolation domain covalently binds the adenylated amino acids to phosphopantetheine, and the condensation domain elongates the peptide chain. Ciclosporin synthetase substrates include L-valine, L-leucine, L-alanine, glycine, 2-aminobutyric acid, 4-methylthreonine, and D-alanine, which is the starting amino acid in the biosynthetic process.