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环孢素A是一种环状十一肽,有抗炎症、抗真菌和抗寄生虫活性,临床上已作为器官移植的首选免疫抑制剂.环孢素A是由真菌Tolypocladium niveum以非核糖体模式产生的,已查明其生物合成至少涉及40个不同的反应步骤,这些反应又均由环孢素合成酶催化的.环孢素合成酶是种多功能酶,分子量约为1500kDa.酶能活化环孢素A的构成氨基酸成为氨基酸基腺苷酸,再通过硫酯键共价地结合它们.在这个阶段里,7种的底物氨基酸,在环孢素合成酶的甲基转移酶功能的作用下,利用AdoMet作为甲基的供体,变成为N-甲基化的产物.肽键形成之后,从酶上释出的环孢素A的分子.作者的研究证明:D-丙氨酸是作为起动氨基酸(Starteraminua acid),是起动合成环孢素所必需的.而D-丙氨酸的提供有赖于一种特异的丙氨酸消旋酶,所以它成为环孢素生物合成的关键酶,对合成起着限速作用(rate-limiting).
Cyclosporin A is a cyclic undecapeptide with anti-inflammatory, anti-fungal and anti-parasite activity and is clinically the preferred immunosuppressant for organ transplantation.Cyclosporin A is produced by the fungus Tolypocladium niveum as a non-ribosomal Mode, it has been identified that its biosynthesis involves at least 40 different reaction steps, all of which are catalyzed by cyclosporine synthase, a multifunctional enzyme with a molecular weight of about 1500 kDa. Enzyme energy The constituent amino acids of activated cyclosporin A become amino acid adenylate, which are then covalently bound by thioester bonds. At this stage, seven of the substrate amino acids, which are functional in the methyltransferase function of cyclosporin synthase , The use of AdoMet as a methyl donor becomes a product of N-methylation.After the formation of a peptide bond, a molecule of cyclosporine A released from the enzyme is studied by the authors.D-C As a starter amino acid (Starteraminua acid), it is necessary to start the synthesis of cyclosporine, and D-alanine depends on a specific alanine racemase so it becomes cyclosporine biosynthesis The key enzyme, for the synthesis of rate-limiting (rate-limiting).