LaeA, a Regulator of Secondary Metabolism in Aspergillus spp

By J. Bok, N. Keller. Eukaryotic Cell, 2004

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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 (ΔlaeA) 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, ΔlaeA 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.

Subfields: Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/928d366e00cf574c73144408d21344d6b3c0923c

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Citations in the corpus

One Juliet and four Romeos: VeA and its methyltransferases (2015, background): “Small bioactive chemicals, also named secondary metabolites (SMs), are produced by several groups of organisms, including fungi, bacteria, and plants (Bok and Keller, 2004; Yu and Keller, 2005; Brakhage, 2013).”
Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus (2005, background): “The genome also contains one copy of laeA encoding a global regulator of Aspergillus secondary metabolites 17 .”
Fungal endophytes: unique plant inhabitants with great promises (2011, background): “The expression of sterigmatocystin, penicillin, and lovastatin gene clusters was blocked upon deletion of LaeA, while its overexpression resulted in increased penicillin and lovastatin production (Bok and Keller 2004).”
Mitochondrial β‐oxidation in Aspergillus nidulans (2004, methodology): “This PCR product was blunt-end cloned into the BamHI site (filled in with T4 polymerase) of pJW53 (Bok and Keller, 2004) to generate pLMH11.”
Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products (2010, background): “On the other hand, overexpression of LaeA triggered increased penicillin and lovastatin production (Bok and Keller 2004).”