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

Metsä-Ketelä M,Palmu K,Kunnari T,Ylihonko K,Mäntsälä P

doi

10.1128/aac.47.4.1291-1296.2003

subject

Has Abstract

pub_date

2003-04-01 00:00:00

pages

1291-6

issue

4

eissn

0066-4804

issn

1098-6596

journal_volume

47

pub_type

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