title: Engineering anthracycline biosynthesis toward angucyclines.
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.
authors.affiliation: Department of Biochemistry, University of Turku, FIN-20014 Turku. Galilaeus Oy, FIN-20781 Kaarina, Finland. mianme@utu.fi
authors.forename: Mikko
authors.initials: M
authors.lastname: Metsä-Ketelä
authors.forename: Kaisa
authors.initials: K
authors.lastname: Palmu
authors.forename: Tero
authors.initials: T
authors.lastname: Kunnari
authors.forename: Kristiina
authors.initials: K
authors.lastname: Ylihonko
authors.forename: Pekka
authors.initials: P
authors.lastname: Mäntsälä
mesh_terms: D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D005818:Genetic Engineering; D005810:Multigene Family; D009621:Nogalamycin / Q000096:biosynthesis*; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; C011157:aclacinomycins; D015250:Aclarubicin; D009621:Nogalamycin