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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.

Citation

S Kakinuma, K Suzuki, M Hatori, K Saitoh, T Hasegawa, T Furumai, T Oki. Biosynthesis of the pradimicin family of antibiotics. III. Biosynthetic pathway of both pradimicins and benanomicins. The Journal of antibiotics. 1993 Mar;46(3):430-40

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PMID: 8478261

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