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.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Metsä-Ketelä M,Palmu K,Kunnari T,Ylihonko K,Mäntsälä Pdoi
10.1128/aac.47.4.1291-1296.2003subject
Has Abstractpub_date
2003-04-01 00:00:00pages
1291-6issue
4eissn
0066-4804issn
1098-6596journal_volume
47pub_type
杂志文章abstract::Aggregatibacter actinomycetemcomitans, a periodontopathogen, has been associated with several systemic diseases. Herein, we report the protective effect of human lactoferrin (hLF) during A. actinomycetemcomitans bacteremia in lactoferrin knockout (LFKO(-/-)) mice. The prophylactic, concurrent, and therapeutic intraven...
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doi:10.1128/AAC.43.12.3011
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journal_title:Antimicrobial agents and chemotherapy
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