BIOSYNTHESIS OF THE ANTIBIOTIC GRANATICIN

The antibiotic granaticin (Ia) is synthesized by Streptomyces violaceoruber from eight acetate units, which are assembled into a benzoisochromane quinone moiety, and a molecule of glucose, which is converted into a 2, 6-dideoxyhexose and attached to the aromatic moiety by carbon-carbon linkages at C-1 and C-4. Conversion of glucose into the 2, 6-dideoxyhexose moiety proceeds with retention of H-1, H-2, H-4, and the hydrogens at C-6 and loss of H-3 and H-5. The hydroxyl group at C-6 of glucose is replaced with inversion of configuration by a hydrogen which is transferred intramolecularly from C-4, indicating operation of the dTDP-glucose oxidoreductase reaction as the first pathway-specific step. The hydroxyl group at C-2 of the hexose is replaced by hydrogen with retention of configuration. The last step in the biosynthesis of granaticin seems to be formation of the five-membered lactone ring; a cell-free extract of S. violaceoruber was shown to catalyze formation of granaticin from dihydrogranaticin (IIa) without incorporation of 18O from 18O2. © 1979, American Chemical Society. All rights reserved.