BIOSYNTHESIS OF THE PRADIMICIN FAMILY OF ANTIBIOTICS .3. BIOSYNTHETIC-PATHWAY OF BOTH PRADIMICINS AND BENANOMICINS

被引:16
作者
KAKINUMA, S [1 ]
SUZUKI, K [1 ]
HATORI, M [1 ]
SAITOH, K [1 ]
HASEGAWA, T [1 ]
FURUMAI, T [1 ]
OKI, T [1 ]
机构
[1] CARE OF OKUMURA J,BRISTOL MYERS SQUIBB RES INST,2-9-3 SHIMO MEGURO,MEGURO KU,TOKYO 153,JAPAN
关键词
D O I
10.7164/antibiotics.46.430
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The biosynthetic pathway of the pradimicin-benanomicin family of antibiotics was investigated by using sinefungin and blocked mutants derived from Actinomadura verrucosospora subsp. neohibisca E-40 (a high pradimicin producer) or Actinomadura sp. AB1236 (a benanomicin producer). Addition of sinefungin to strain E-40, pradimicin A aglycone-producing mutant or strain AB1236 inhibited the formation of 11-O-demethyl-7-methoxypradinone II (11dM-7M-PN II), resulting in the accumulation of 11-O-demethylpradimicinone II and pradimicinone II. By feeding pradimicin A aglycone and its analogs to mutants blocked early in pradimicin or benanomicin biosynthesis, the following results were obtained: 11-O-demethylpradinone II, 11dM-7M-PN II, 11-O-demethylpradinone I, 11-O-demethylpradimicinone I and pradimicinone I were converted to pradimicin A or benanomicin A; the remaining 6 aglycone analogs were not incorporated into the antibiotics. Pradimicin B, dexylosylpradimicin C and dexylosylbenanomicin A were converted to pradimicin A, pradimicin C and benanomicin A, respectively. A biosynthetic pathway for the antibiotics is proposed.
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页码:430 / 440
页数:11
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