The biosynthetic pathway for aurofusarin in Fusarium graminearum reveals a close link between the naphthoquinones and naphthopyrones

Summary Fungal polyketide biosynthesis typically involves multiple enzymatic steps and the encoding genes are often found in gene clusters. A gene cluster containing PKS12, the polyketide synthase gene responsible for the synthesis of the pigment aurofusarin, was analysed by gene replacement using A...

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Bibliographic Details
Published in:Molecular microbiology 2006-08, Vol.61 (4), p.1069-1080
Main Authors: Frandsen, Rasmus J. N., Nielsen, Nikoline J., Maolanon, Nicolai, Sørensen, Jens C., Olsson, Stefan, Nielsen, John, Giese, Henriette
Format: Article
Language:English
Subjects:
Agrobacterium
Agrobacterium tumefaciens - genetics
Biological and medical sciences
Cluster analysis
Enzymes
Fundamental and applied biological sciences. Psychology
Fungal Proteins - chemistry
Fungal Proteins - genetics
Fungal Proteins - metabolism
Fungi
Fusarium - genetics
Fusarium - metabolism
Fusarium graminearum
Genes
Genes, Fungal
Microbiology
Miscellaneous
Molecules
Mutation
Mycology
Naphthalenes - chemistry
Naphthalenes - metabolism
Naphthoquinones - chemistry
Naphthoquinones - metabolism
Transcription Factors - genetics
Transformation, Bacterial
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Summary:Summary Fungal polyketide biosynthesis typically involves multiple enzymatic steps and the encoding genes are often found in gene clusters. A gene cluster containing PKS12, the polyketide synthase gene responsible for the synthesis of the pigment aurofusarin, was analysed by gene replacement using Agrobacterium tumefaciens‐mediated transformation to determine the biosynthesis pathway of aurofusarin. Replacement of aurR1 with hygB shows that it encodes a positively acting transcription factor that is required for the full expression of PKS12, aurJ, aurF, gip1 and FG02329.1, which belong to the gene cluster. AurR1 and PKS12 deletion mutants are unable to produce aurofusarin and rubrofusarin. Bio‐ and chemoinformatics combined with chemical analysis of replacement mutants (ΔaurJ, ΔaurF, Δgip1, ΔaurO and ΔPKS12) indicate a five‐step enzyme catalysed pathway for the biosynthesis of aurofusarin, with rubrofusarin as an intermediate. This links the biosynthesis of naphthopyrones and naphthoquinones together. Replacement of the putative transcription factor aurR2 results in an increased level of rubrofusarin relative to aurofusarin. Gip1, a putative laccase, is proposed to be responsible for the dimerization of two oxidized rubrofusarin molecules resulting in the formation of aurofusarin.
ISSN:0950-382X
1365-2958
DOI:10.1111/j.1365-2958.2006.05295.x