Biosynthesis of the red pigment bikaverin in Fusarium fujikuroi: genes, their function and regulation

• Published in: Molecular microbiology Vol. 72; no. 4; pp. 931 - 946
• Main Authors: Wiemann, Philipp, Willmann, Anita, Straeten, Marcus, Kleigrewe, Karin, Beyer, Marita, Humpf, Hans-Ulrich, Tudzynski, Bettina
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.05.2009; Blackwell Publishing Ltd; Blackwell
• Subjects: Bacterial proteins; Biological and medical sciences; Biosynthesis; Fundamental and applied biological sciences. Psychology; Fungal Proteins - genetics; Fungal Proteins - metabolism; Fusarium - genetics; Fusarium - metabolism; Gene expression; Gene Expression Regulation, Fungal; Gene Targeting; Genes; Genes, Fungal; Genetic Complementation Test; Genomic Library; Hydrogen-Ion Concentration; Metabolism; Metabolites; Microbiology; Miscellaneous; Molecular Structure; Multigene Family; Mycology; Nitrogen - metabolism; Pigments, Biological - biosynthesis; Protein synthesis; Secondary metabolites; Studies; Time Factors; Transcription Factors - metabolism; Xanthones - metabolism; Fungi; Plant pathogen; Gene; Microbiology; Pigments; Biosynthesis; Fungi Imperfecti
• ISSN: 0950-382X; 1365-2958; 1365-2958
• DOI: 10.1111/j.1365-2958.2009.06695.x

Fusarium secondary metabolites are structurally diverse, have a variety of activities and are generally poorly understood biosynthetically. The F. fujikuroi polyketide synthase gene bik1 was previously shown to be responsible for formation of the mycelial pigment bikaverin. Here we present the characterization of five genes adjacent to bik1 as encoding a putative FAD-dependent monooxygenase (bik2), an O-methyltransferase (bik3), an NmrA-like protein (bik4), a Zn(II)₂Cys₆ transcription factor (bik5) and an MFS transporter (bik6). Deletion of each gene resulted in total loss or significant reduction of bikaverin synthesis. Expression studies revealed that all bik genes are repressed by high amounts of nitrogen in an AreA-independent manner and are subject to a time- and pH-dependent regulation. Deletion of the pH regulatory gene pacC resulted in partial derepression while complementation with a dominant active allele resulted in repression of bik genes at acidic ambient pH. Transcription of all bik genes in strains lacking bik1, bik2 or bik3 was essentially eliminated, while transcription of some bik genes was detected in strains lacking bik4, bik5 or bik6. Thus, bikaverin synthesis is regulated by a complex regulatory network. Understanding how different factors influence the synthesis of this model secondary metabolite will aid understanding secondary metabolism in general.