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Biosynthesis and Role in Virulence of the Histone Deacetylase Inhibitor Depudecin from Alternaria brassicicola

October 2009 , Volume 22 , Number  10
Pages  1,258 - 1,267

Wanessa D. Wight,1 Kwang-Hyung Kim,2 Christopher B. Lawrence,2 and Jonathan D. Walton1

1Department of Energy - Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, U.S.A.; 2Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, VA 24061, U.S.A.

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Accepted 25 May 2009.

Depudecin, an eleven-carbon linear polyketide made by the pathogenic fungus Alternaria brassicicola, is an inhibitor of histone deacetylase (HDAC). A chemically unrelated HDAC inhibitor, HC toxin, was earlier shown to be a major virulence factor in the interaction between Cochliobolus carbonum and its host, maize. In order to test whether depudecin is also a virulence factor for A. brassicicola, we identified the genes for depudecin biosynthesis and created depudecin-minus mutants. The depudecin gene cluster contains six genes (DEP1 to DEP6), which are predicted to encode a polyketide synthase (AbPKS9 or DEP5), a transcription factor (DEP6), two monooxygenases (DEP2 and DEP4), a transporter of the major facilitator superfamily (DEP3), and one protein of unknown function (DEP1). The involvement in depudecin production of DEP2, DEP4, DEP5, and DEP6 was demonstrated by targeted gene disruption. DEP6 is required for expression of DEP1 through DEP5 but not the immediate flanking genes, thus defining a coregulated depudecin biosynthetic cluster. The genes flanking the depudecin gene cluster but not the cluster itself are conserved in the same order in the related fungi Stagonospora nodorum and Pyrenophora tritici-repentis. Depudecin-minus mutants have a small (10%) but statistically significant reduction in virulence on cabbage (Brassica oleracea) but not on Arabidopsis. The role of depudecin in virulence is, therefore, less dramatic than that of HC toxin.

© 2009 The American Phytopathological Society