Abstract
Secondary metabolites, or biochemical indicators of fungal development, are of intense interest to humankind due to their pharmaceutical and/or toxic properties. We present here a novel Aspergillus nuclear protein, LaeA, as a global regulator of secondary metabolism in this genus. Deletion of laeA (DeltalaeA) blocks the expression of metabolic gene clusters, including the sterigmatocystin (carcinogen), penicillin (antibiotic), and lovastatin (antihypercholesterolemic agent) gene clusters. Conversely, overexpression of laeA triggers increased penicillin and lovastatin gene transcription and subsequent product formation. laeA expression is negatively regulated by AflR, a sterigmatocystin Zn2Cys6 transcription factor, in a unique feedback loop, as well as by two signal transduction elements, protein kinase A and RasA. Although these last two proteins also negatively regulate sporulation, DeltalaeA strains show little difference in spore production compared to the wild type, indicating that the primary role of LaeA is to regulate metabolic gene clusters.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Aspergillus / enzymology*
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Aspergillus / metabolism
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Binding Sites
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Cloning, Molecular
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / metabolism
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Fungal Proteins / genetics*
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Fungal Proteins / metabolism
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Fungal Proteins / physiology*
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Gene Expression Regulation, Fungal
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Lovastatin / biosynthesis
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Lovastatin / genetics
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Molecular Sequence Data
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Multigene Family / genetics
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Mycelium / genetics
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Mycelium / metabolism
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Penicillins / biosynthesis
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Pigmentation / genetics
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Promoter Regions, Genetic
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Protein Methyltransferases / genetics*
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Protein Methyltransferases / metabolism
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Protein Methyltransferases / physiology*
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Sequence Alignment
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Spores, Fungal / genetics
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Spores, Fungal / metabolism
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Sterigmatocystin / biosynthesis
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Transcription Factors / metabolism
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ras Proteins / metabolism
Substances
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AFLR protein, Aspergillus
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DNA-Binding Proteins
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Fungal Proteins
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Penicillins
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Transcription Factors
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Sterigmatocystin
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Lovastatin
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Protein Methyltransferases
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Cyclic AMP-Dependent Protein Kinases
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ras Proteins