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Eukaryotic Cell, April 2004, p. 527-535, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.527-535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

LaeA, a Regulator of Secondary Metabolism in Aspergillus spp.

Jin Woo Bok and Nancy P. Keller*

Department of Plant Pathology, University of Wisconsin—Madison, Madison, Wisconsin 53706

Received 5 November 2003/ Accepted 16 December 2003

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 ({Delta}laeA) 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, {Delta}laeA 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.

* Corresponding author. Mailing address: Department of Plant Pathology, University of Wisconsin, 1630 Linden Dr., Madison, WI 53706. Phone: (608) 262-9795. Fax: (608) 263-2626. E-mail: npk{at}plantpath.wisc.edu.

Eukaryotic Cell, April 2004, p. 527-535, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.527-535.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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