Enzymatic synthesis of cyclosporin A.
An enzyme fraction, isolated from crude extracts of the fungus Tolypocladium inflatum, strain 7939/F, is able to synthesize the undecapeptide cyclosporin A. The formation of cyclosporin A was monitored by incorporation of the radiolabeled constituent amino acids of cyclosporin A or by using S-adenosyl-L-[14C-methyl] methionine. The structure of cyclosporin A, synthesized enzymatically in vitro, was confirmed by chromatographic comparison with the authentic compound and by amino acid analyses. Replacement of L-2-aminobutyric acid in the reaction mixture by L-alanine, L-threonine, L-valine, or L-norvaline yields the naturally occurring cyclosporins B, C, D, and G. Also, D-alanine could be replaced by D-serine to yield [D-Ser8]cyclosporin A.
Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, Federal Republic of Germany.
A
A
Billich
R
R
Zocher
D000596:Amino Acids / Q000378:metabolism; D016572:Cyclosporine; D003524:Cyclosporins / Q000096:biosynthesis* / Q000302:isolation & purification; D003904:Mitosporic Fungi / Q000201:enzymology*
D000596:Amino Acids; D003524:Cyclosporins; C100000:cyclosporin C; C045571:cyclosporin G; D016572:Cyclosporine; C050026:cyclosporin D