A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Engineering anthracycline biosynthesis toward angucyclines
Tekijät: Metsa-Ketela M, Palmu K, Kunnari T, Ylihonko K, Mantsala P
Kustantaja: AMER SOC MICROBIOLOGY
Julkaisuvuosi: 2003
Lehti:Antimicrobial Agents and Chemotherapy
Tietokannassa oleva lehden nimiANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Lehden akronyymi: ANTIMICROB AGENTS CH
Vuosikerta: 47
Numero: 4
Aloitussivu: 1291
Lopetussivu: 1296
Sivujen määrä: 6
ISSN: 0066-4804
DOI: https://doi.org/10.1128/AAC.47.4.1291-1296.2003
Tiivistelmä
The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6. Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis. This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring.
The biosynthesis pathways of two anthracyclines, nogalamycin and aclacinomycin, were directed toward angucyclines by using an angucycline-specific cyclase, pgaF, isolated from a silent antibiotic biosynthesis gene cluster. Addition of pgaF to a gene cassette that harbored the early biosynthesis genes of nogalamycin resulted in the production of two known angucyclinone metabolites, rabelomycin and its precursor, UWM6. Substrate flexibility of pgaF was demonstrated by replacement of the nogalamycin minimal polyketide synthase genes in the gene cassette with the equivalent aclacinomycin genes together with aknE2 and aknF, which specify the unusual propionate starter unit in aclacinomycin biosynthesis. This modification led to the production of a novel angucyclinone, MM2002, in which the expected ethyl side chain was incorporated into the fourth ring.
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