title: Regulation of cyclic peptide biosynthesis and pathogenicity in Cochliobolus carbonum by TOXEp, a novel protein with a bZIP basic DNA-binding motif and four ankyrin repeats.
abstract: HC-toxin is an epoxide-containing cyclic tetrapeptide that is a critical virulence determinant in the pathogenic interaction between the filamentous fungus Cochliobolus carbonum and maize. HC-toxin exerts a potent cytostatic effect on plant and animal cells by inhibiting histone deacetylase. The biosynthesis of HC-toxin by C. carbonum is controlled by a complex genetic locus, TOX2, that contains multiple, duplicated copies of genes encoding export and biosynthetic enzymes. A new gene in the TOX2 complex, TOXE, has now been isolated. Mutation of TOXE by targeted gene disruption has no effect on growth and sporulation but abolishes HC-toxin production and pathogenicity. TOXE is required for the expression of three genes with a known or putative role in HC-toxin production, but is not required for expression of HTS1, which encodes the large, multifunctional peptide synthetase that is the central enzyme in HC-toxin biosynthesis. At its N-terminus, TOXEp has a bZIP basic DNA binding domain, but it does not contain any discernible leucine zipper or helix-loop-helix. At its carboxy terminus, TOXEp contains four ankyrin repeats. In having these two common regulatory motifs in a single polypeptide, TOXEp appears to represent a novel class of regulatory protein. TOXE is present only in HC-toxin-producing (Tox2+) isolates of C. carbonum. Most Tox2+ isolates have two copies: in strain SB111, one copy of TOXE is on the same 3.5-Mb chromosome that contains all of the other genes known to be involved in HC-toxin biosynthesis, and the second copy of TOXE is on a 0.7-Mb chromosome.
authors.affiliation: Department of Energy-Plant Research Laboratory, Michigan State University, E. Lansing 48824, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Ahn
authors.forename: J D
authors.initials: JD
authors.lastname: Walton
mesh_terms: D000595:Amino Acid Sequence; D017487:Ankyrins; D001203:Ascomycota / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D017421:Sequence Analysis
chemical_list: D017487:Ankyrins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D010456:Peptides, Cyclic; C100779:TOXA protein, Cochliobolus carbonum; C116821:TOXE protein, Cochliobolus carbonum; C037654:HC toxin