title: Complex regulation of secondary metabolism controlling pathogenicity in the phytopathogenic fungus Alternaria alternata.
abstract: The filamentous fungus Alternaria alternata includes seven pathogenic variants (pathotypes), which produce different host-selective toxins and cause disease on different plants. The Japanese pear, strawberry and tangerine pathotypes produce AK-toxin, AF-toxin and ACT-toxin, respectively, which have a common structural moiety, 9,10-epoxy-8-hydroxy-9-methyl-decatrienoic acid (EDA). Here, we identified a new gene, AKT7 (AK-toxin biosynthetic gene 7), from the Japanese pear pathotype, which encodes a cytochrome P450 monooxygenase and functions to limit AK-toxin production. AKT7 homologs were found in the strawberry pathotype, but not the tangerine pathotype. However, the strawberry pathotype homolog appeared to include a premature stop codon. Although the Japanese pear pathotype strain has multiple copies of AKT7, a single-copy disruption resulted in mutants with increased production of AK-toxin and EDA. AKT7 overexpression in the three pathotypes caused marked reductions of toxin and EDA production, suggesting that Akt7 catalyzes a side reaction of EDA or its precursor. AKT7 overexpression caused reduced virulence in these pathotypes. We also found that AKT7 transcripts predominantly include misspliced mRNAs, which have premature stop codons. Our observations suggest that the AK-toxin production required for full virulence is regulated in a complex way by the copy number and intron information content of AKT7.
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Takaoka
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Harimoto
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Hatta
authors.affiliation: Graduate School of Environmental and Life Science, Okayama University, Okayama, 700-8530, Japan.
authors.forename: Mikihiro
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Faculty of Agriculture, Kagawa University, Miki, Kagawa, 761-0795, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Akimitsu
authors.affiliation: Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya, 464-8601, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuge
mesh_terms: D000528:Alternaria / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D001483:Base Sequence; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D018628:Gene Dosage; D015870:Gene Expression; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D010935:Plant Diseases / Q000382:microbiology*; D018515:Plant Leaves / Q000382:microbiology; D031989:Pyrus / Q000382:microbiology; D012326:RNA Splicing; D064210:Secondary Metabolism; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D009183:Mycotoxins
keywords: Alternaria alternata; biosynthetic gene cluster; cytochrome P450 monooxygenase; host-selective toxin; secondary metabolism; splicing error