A1 Refereed original research article in a scientific journal
Engineering anthracycline biosynthesis toward angucyclines
Authors: Metsa-Ketela M, Palmu K, Kunnari T, Ylihonko K, Mantsala P
Publisher: AMER SOC MICROBIOLOGY
Publication year: 2003
Journal:Antimicrobial Agents and Chemotherapy
Journal name in sourceANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Journal acronym: ANTIMICROB AGENTS CH
Volume: 47
Issue: 4
First page : 1291
Last page: 1296
Number of pages: 6
ISSN: 0066-4804
DOI: https://doi.org/10.1128/AAC.47.4.1291-1296.2003
Abstract
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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