INVESTIGATIONS OF THE BIOSYNTHESIS OF ARISTEROMYCIN (NEPLANOCIN A)
Doctor of Philosophy
The biosynthesis of the antibiotic aristeromycin (1), produced by Streptomyces citricolor, has been investigated. Incorporation experiments using (('13)C)- and ('3)H, ('14)C -labelled forms of glucose have shown that the carbocyclic portion of aristeromycin is derived from glucose. Further studies revealed some interesting mechanistic details of the ring formation. Precursor incorporation studies have also shown that the adenine moiety from adenosine is incorporated intact into the antibiotic. Administration of (1,2-('13)C(,2))-glycine and (2-('13)C,('15)N)-glycine has shown that C-2 of glycine is incorporated into C-2, C-5, and C-8 and C-1 of glycine into C-4 of the adenine moiety of aristeromycin. The antibiotic and antitumor agent neplanocin A (4) has been successfully isolated from S. citricolor, and results from precursor incorporation experiments suggest that the biosyntheses of aristeromycin and neplanocin A are closely related.