BIOSYNTHESIS OF THE ANTIBIOTIC GRANATICIN

被引:64
作者
SNIPES, CE [1 ]
CHANG, C [1 ]
FLOSS, HG [1 ]
机构
[1] PURDUE UNIV,SCH PHARM & PHARM SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907
关键词
D O I
10.1021/ja00497a036
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
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页码:701 / 706
页数:6
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