Biosynthesis of the pradimicin family of antibiotics. III. Biosynthetic pathway of both pradimicins and benanomicins.
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.
Kakinuma
S
S
Bristol-Myers Squibb Research Institute, Tokyo, Japan.
Suzuki
K
K
Hatori
M
M
Saitoh
K
K
Hasegawa
T
T
Furumai
T
T
Oki
T
T
D000192:Actinomycetales / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D000935:Antifungal Agents / Q000096:biosynthesis* / Q000494:pharmacology; D005285:Fermentation; D009154:Mutation
D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D000241:Adenosine; C006235:sinefungin