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].
Research Article| June 01 1994
In vitro biosynthesis of ring-extended cyclosporins
*Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, Franklinstr. 29, D-10587 Berlin, and Max-Planck-Gesellschaft zur Forderung der Wissenchaften, AG “Enzymologie der Peptidbindung”, Weinbergweg 16a, D-06120 Halle, Germany,
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Biochem J (1994) 300 (2): 395–399.
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A Lawen, R Traber, R Reuille, M Ponelle; In vitro biosynthesis of ring-extended cyclosporins. Biochem J 1 June 1994; 300 (2): 395–399. doi: https://doi.org/10.1042/bj3000395
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