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Curr Genet. 1994 Feb;25(2):95-100.

Identification of the yeast ACC1 gene product (acetyl-CoA carboxylase) as the target of the polyketide fungicide soraphen A.

Author information

1
Ciba-Geigy AG, Biotechnology Department K-681.109, Basel, Switzerland.

Abstract

Soraphen A, a polyketide isolated from the myxobacterium Sorangium cellulosum, is a potent inhibitor of fungal growth. We have used a genetic approach to localize the target of this drug, employing Saccharomyces cerevisiae as a model organism. we have isolated soraphen A-resistant mutants and found that all of them map at the same genetic locus and exhibit a broad range of semidominant phenotypes. Data from genetic crosses of soraphen A-resistant clones with an acc1 mutant revealed that ACC1, coding for acetyl-CoA carboxylase (E.C. 6.4.1.2), is tightly linked to soraphen A resistance. Partially-purified enzyme extracts containing acetyl-CoA carboxylase were prepared and assayed for their soraphen A sensitivity. Our experiments showed that the catalytic activity of the wild-type enzyme is inhibited in vitro by soraphen A while the mutant enzyme remains catalytically active. Taken together these data strongly suggest that the ACC1 gene product is the primary target for soraphen A in vivo.

PMID:
7916271
DOI:
10.1007/bf00309532
[Indexed for MEDLINE]

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