title: The cross-pathway control system regulates production of the secondary metabolite toxin, sirodesmin PL, in the ascomycete, Leptosphaeria maculans.
abstract: BACKGROUND
  Sirodesmin PL is a secondary metabolite toxin made by the ascomycetous plant pathogen, Leptosphaeria maculans. The sirodesmin biosynthetic genes are clustered in the genome. The key genes are a non-ribosomal peptide synthetase, sirP, and a pathway-specific transcription factor, sirZ. Little is known about regulation of sirodesmin production.
  
  
  RESULTS
  Genes involved in regulation of sirodesmin PL in L. maculans have been identified. Two hundred random insertional T-DNA mutants were screened with an antibacterial assay for ones producing low levels of sirodesmin PL. Three such mutants were isolated and each transcribed sirZ at very low levels. One of the affected genes had high sequence similarity to Aspergillus fumigatus cpcA, which regulates the cross-pathway control system in response to amino acid availability. This gene was silenced in L. maculans and the resultant mutant characterised. When amino acid starvation was artificially-induced by addition of 3-aminotriazole for 5 h, transcript levels of sirP and sirZ did not change in the wild type. In contrast, levels of sirP and sirZ transcripts increased in the silenced cpcA mutant. After prolonged amino acid starvation the silenced cpcA mutant produced much higher amounts of sirodesmin PL than the wild type.
  
  
  CONCLUSIONS
  Production of sirodesmin PL in L. maculans is regulated by the cross pathway control gene, cpcA, either directly or indirectly via the pathway-specific transcription factor, sirZ.
authors.affiliation: School of Botany, University of Melbourne, Victoria, (3010), Australia. ce@unimelb.edu.au
authors.forename: Candace E
authors.initials: CE
authors.lastname: Elliott
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Fox
authors.forename: Renee S
authors.initials: RS
authors.lastname: Jarvis
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Howlett
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001203:Ascomycota / Q000235:genetics* / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics; D053898:Biosynthetic Pathways / Q000235:genetics*; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010879:Piperazines / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D000596:Amino Acids; D050976:Basic-Leucine Zipper Transcription Factors; D004271:DNA, Fungal; D010879:Piperazines; C014187:sirodesmin