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

• Published in: Journal of antibiotics Vol. 46; no. 3; pp. 430 - 440
• Main Authors: KAKINUMA, SHIZUKO, SUZUKI, KIYOSHI, HATORI, MASAMI, SAITOH, KYOICHIRO, HASEGAWA, TOSHIFUMI, FURUMAI, TAMOTSU, OKI, TOSHIKAZU
• Format: Journal Article
• Language: English
• Published: Tokyo JAPAN ANTIBIOTICS RESEARCH ASSOCIATION 1993; Japan Antibiotics Research Association
• Subjects: Actinomadura verrucosospora; Actinomycetales - drug effects; Actinomycetales - genetics; Actinomycetales - metabolism; Adenosine - analogs & derivatives; Adenosine - pharmacology; Antibiotics (antibacterial agents, antifungal agents); Antibiotics, Antineoplastic - biosynthesis; Antibiotics, microbial producers, chemotherapic agents, antiseptics, disinfecting agents; Antifungal Agents - biosynthesis; Antifungal Agents - pharmacology; Applied microbiology; Biological and medical sciences; Fermentation; Fundamental and applied biological sciences. Psychology; Microbiology; Mutation; Molecular structure; Nocardiaceae; Biosynthesis; Actinomadura; Fermentation; In vitro; Actinomycetales; Antibiotic; Antifungal agent; Microbial origin; Biotransformation; Production; Microorganism culture; Bacteria; Antiviral; Isolation; Actinomycetes
• ISSN: 0021-8820; 1881-1469
• DOI: 10.7164/antibiotics.46.430

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.