[[image:BScyclosporin2.png|thumb|frame|left|Figure 1:  Cyclosporine A Biosynthesis.  Bmt = butenylmethylthreonine, Abu = L-alpha-aminobutyric acid, Sar = sarcosine]]

Cyclosporine A is synthesized by a [[nonribosomal peptide]] synthetase, cyclosporine synthetase.   The enzyme contains an adenylation domain, thiolation domain, condensation domain, and an N-methyltransferase domain. The adenylation domain is responsible for substrate recognition and activation. While the thiolation domain covalently binds the adenylated amino acids to phosphopantetheine and the condensation domain elongates the peptide chain.  Cyclosporine synthetase substrates includes: L-[[Valine]], L-[[Leucine]], L-[[Alanine]], L-[[Glycine]], 2-aminobutyric acid, 4-methylthreonine, and D-Alanine. With the adenylation domain, cyclosporine synthetase generates the acyl adenylated [[amino acids[[ then covalently binds the amino acid to phosphopantetheine through a thioester linkage. Some of the amino acid substrates become N-methylated by S-adenosylmethionine. The cyclization step releases cyclosporine A from the enzyme. <ref> Hoppert, M.; Gentzsch, C.; SchÓ§rgendorfer, K.  Arch. Microbiol.  2001, 176, 285-293.</ref> Amino acids such as D-Ala and butenyl-methyl-L-threonine indicates that cyclosporine synthetase requires the action of other enzymes such as a D-Alanine racemase.  The racemization of L-Ala to D-Ala is PLP dependent.  The formation of butenyl-methyl-L-threonine is performed by a butenyl-methyl-L-threonine polyketide synthase that utilizes acetate/malonate as its starting material. <ref> Dewick, P. (2001) Medicinal Natural Products. John Wiley & Sons, Ltd. 2nd ed. </ref>[[image:Bmtsyn2.png|frame|300px|Figure 2:  Butenyl-methyl-L-Threonine Biosynthesis]]