Patent ID: 7427484

Claim:
A method for identifying a novel secondary metabolite biosynthesis gene cluster in a fungus, said method comprising steps of: a) obtaining a transformed fungus having a disrupted laeA gene wherein said laeA gene before disruption comprises a nucleotide sequence that encodes a nuclear protein methyltransferase and that hybridizes under stringent conditions, comprising overnight hybridization at 42° C. in 50% formamide with 1 mg heparin followed by a 15 minute wash at 65° C. in 0.2x SSC, to either strand of a denatured double-stranded nucleic acid having the nucleotide sequence set forth in SEQ ID NO:2; and wherein expression of the non-disrupted laeA gene in a fungal host cell results in the increased production of a polypeptide capable of regulating a gene cluster specifying the production of at least one secondary metabolite selected from a polyketide, a non-ribosomal peptide and a hyphal pigment and expression of a disrupted laeA gene results in the production of an inactive laeA polypeptide or its absence; (b) isolating a sample of nucleic acids from the transformed fungus of step (a), said sample of nucleic acids representative of the expressed genes of the transformed fungus; (c) hybridizing the sample of nucleic acids isolated in step (b) with an array comprising a plurality of nucleic acids representative of the expressed genes of a non-transformed fungus under conditions to form one or more hybridization complexes; (d) detecting said hybridization complexes: (e) comparing the levels of the hybridization complexes detected in step (c) with the level of hybridization complexes detected in a sample of nucleic acids isolated from an laeA-expressing fungus and representative of the expressed genes of the laeA-expressing fungus, wherein an altered level of hybridization complexes detected in step (c) compared with a level of hybridization complexes of the sample of the nucleic acids from the laeA-expressing fungus correlates with an identifies at least one gene under regulatory control of the laeA gene product; and (f) examining genomic nucleotide sequence surrounding said gene identified in step (e) to determine if said gene is clustered with secondary metabolite biosynthesis genes thereby identifying a novel secondary metabolite biosynthesis gene cluster.