Aspergillus nidulans: a Model for Elucidation of Aspergillus fumigatus Secondary Metabolism

Nancy Keller

doi:10.1128/9781555815776.ch17

Chapter 17 : Aspergillus nidulans: a Model for Elucidation of Aspergillus fumigatus Secondary Metabolism

Author: Nancy Keller¹

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Affiliations: 1: Department of Plant Pathology, University of Wisconsin–Madison, Madison, WI 53706

Content Type: Monograph

Publication Year: 2006

Category: Fungi and Fungal Pathogenesis

Book DOI: 10.1128/9781555815776

Chapter DOI: 10.1128/9781555815776.ch17

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Abstract:

This chapter reviews the contributions made by Aspergillus nidulans to the understanding of fungal secondary metabolism and the ways in which advances in our understanding of this species have spurred parallel studies of Aspergillus fumigatus. The most thorough insight into fungal secondary metabolite regulation has arisen from studies of the mycotoxin sterigmatocystin (ST) and the antibiotic penicillin in A. nidulans. With possibly the exception of the penicillin metabolic cluster, the most thoroughly examined fungal secondary-metabolite gene clusters are those involved in mycotoxin biosynthesis, particularly the aflatoxin (AF) and ST biosynthetic clusters found in several Aspergillus spp. Coordinate regulation is largely explained by transcriptional control by pathway-specific regulatory factors (e.g., aflR) and global regulatory proteins including transcription factors mediating environmental signals (pH, carbon, and nitrogen) and the cluster-specific methylase, LaeA. Specific oxylipins, e.g., various prostaglandins, are ligands to G-protein-coupled receptors (GPCR), which are important in inflammatory and immune responses in mammals. Interestingly, recent studies have identified three A. nidulans GPCR that impact asexual and sexual spore production, and efforts are under way to determine if Ppo products may be potential ligands for these receptors. PGs, along with leukotrienes, comprise a class of oxylipins called eicosanoids formed from C20 fatty acids (dihomo-γ-linolenic acid, arachidonic acid, and eicosanopentaenoic acid). Initial studies of laeA and ppo function in A. fumigatus indicate a potent role for these secondarymetabolite genes in pathogenesis. A thorough understanding of the function of these and other secondary metabolism genes may assist in the development of future therapeutics.

Citation: Keller N. 2006. Aspergillus nidulans: a Model for Elucidation of Aspergillus fumigatus Secondary Metabolism, p 235-243. In Heitman J, Filler S, Edwards, Jr. J, Mitchell A (ed), Molecular Principles of Fungal Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555815776.ch17

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Aspergillus nidulans: a Model for Elucidation of Aspergillus fumigatus Secondary Metabolism

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Figure 1.

A. nidulans ST (A) and A. fumigatus gliotoxin (B) gene clusters. The function of each protein is listed. AF, aflatoxin.

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Figure 1.

A. nidulans ST (A) and A. fumigatus gliotoxin (B) gene clusters. The function of each protein is listed. AF, aflatoxin.

/content/10.1128/9781555815776.ch17.ch17fig02

Figure 2.

(A) Thin-layer chromatography of organic extracts of the A. nidulans and A. fumigatus ΔlaeA mutants compared to the wild type (WT). ST, sterigmatocystin standard: G, gliotoxin standard. Note that both ΔlaeA mutants are deficient in the production of many metabolites, not just ST (A. nidulans) or G (A. fumigatus). (B) Northern analysis of sterigmatocystin genes, aflR and stcU, in A. nidulans wild-type and ΔlaeA strains at the 12-, 24-, 48-, and 72-h time points. Expression of both genes is repressed in the ΔlaeA mutant. Reprinted from reference 3 with permission.

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Figure 2.

/content/10.1128/9781555815776.ch17.ch17fig03

Figure 3.

Proposed model of G-protein signaling in regulating sporulation and mycotoxin biosynthesis in Aspergillus spp. Oxylipin acts as a ligand to initiate the G-protein signaling cascade, which can lead to either suppression of toxin formation and sporulation (shown here) or activation of both processes (via different GPCR and different α subunits of the heterotrimeric G proteins). FadA, alpha subunit of a heterotrimeric G protein; FlbA, RGS protein; PkaA, protein kinase A; LaeA, global regulator of secondary metabolites.

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Figure 3.

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