Lawen A, Traber R, Reuille R, Ponelle M
Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, Germany.
Biochem J. 1994 Jun 1;300 ( Pt 2)(Pt 2):395-9. doi: 10.1042/bj3000395.
Cyclosporin synthetase, a multifunctional polypeptide, catalyses the biosynthesis of the set of natural cyclosporins. We report that this enzyme is also capable of introducing a beta-alanine into position 7 or 8 of the ring instead of the alpha-alanines present at these positions in cyclosporin A. This leads to 34-membered rings in contrast to the 33-membered ring of the cyclo-undecapeptide cyclosporin A. Both [beta Ala7]CyA and [beta Ala8]CyA show immunosuppressive activity. The cyclosporin synthetase-related enzyme peptolide SDZ 214-103 synthetase, on the other hand, does not incorporate either beta-alanine into position 7 or beta-hydroxy acids into position 8, confirming the previously described higher substrate specificity of this enzyme compared with cyclosporin synthetase [Lawen and Traber (1993) J. Biol. Chem. 268, 20452-20465].
环孢菌素合成酶是一种多功能多肽，催化天然环孢菌素的生物合成。我们报告，该酶还能够将β-丙氨酸引入环的第7或第8位，而不是环孢菌素A中这些位置上存在的α-丙氨酸。这导致形成34元环，与环十一肽环孢菌素A的33元环相反。[βAla7]CyA和[βAla8]CyA均显示出免疫抑制活性。另一方面，与环孢菌素合成酶相关的酶肽内酯SDZ 214-103合成酶既不将β-丙氨酸掺入第7位，也不将β-羟基酸掺入第8位，这证实了先前描述的该酶与环孢菌素合成酶相比具有更高的底物特异性[劳恩和特拉伯（1993年）《生物化学杂志》268, 20452 - 20465]。
