Secondary metabolism: regulation and role in fungal biology
Introduction
Classes of fungal secondary metabolites include polyketides (e.g. aflatoxin and fumonisins), non-ribosomal peptides (e.g. sirodesmin, peramine and siderophores such as ferricrocin), terpenes (e.g. T-2 toxin, deoxynivalenol (DON)), indole terpenes (e.g. paxilline and lolitrems) (Figure 1). Genes for the biosynthesis of secondary metabolites are usually clustered [1]; hence they have been identified relatively easily from complete genome sequences. The regulation of secondary metabolism in fungi has been comprehensively reviewed [2, 3••, 4]. This article highlights progress in this field during the last couple of years and describes findings from recent experiments aimed at determining the role of secondary metabolites in fungal biology.
Section snippets
Regulatory genes for biosynthesis of secondary metabolites
Secondary metabolite gene clusters often contain a transcription factor that acts specifically on genes within the cluster. Recently it has become apparent that these regulators may also act on genes elsewhere in the genome. For example, the transcription factor aflR that regulates aflatoxin clusters in Aspergillus flavus and A. parasiticus and the sterigmatocystin cluster of A. nidulans [5, 6, 7, 8, 9], also regulates three genes outside the aflatoxin gene cluster [10]. Microarray experiments
Manipulating expression of regulatory factors to discover novel secondary metabolites
Functional analysis of biosynthetic gene clusters usually relies on disrupting key genes in the cluster and examining the resulting secondary metabolic profile. However, genes in many clusters are expressed at extremely low levels and often particular metabolites cannot be detected in fungi cultured under standard conditions [39]. Comparison of transcriptional profiling of deletion mutants and overexpressors of global regulators of secondary metabolite production has been used to identify the
Role of fungal secondary metabolites in fungal biology
The role that secondary metabolites play in the biology of fungi is elusive. Many such molecules are produced by pathogenic fungi. For instance, an as yet unidentified secondary metabolite produced by some isolates of the rice blast fungus Magnaporthe grisea, is involved in recognition of particular resistant rice cultivars. This metabolite is synthesized by the ACE1 gene cluster, which contains a hybrid polyketide synthase/non-ribosomal peptide synthetase and displays an infection-specific
Concluding remarks and future directions
The regulation of secondary metabolism in fungi is complex, involving multiple proteins and complexes that respond to various environmental and host stimuli. Great inroads have been made into the understanding of these processes in the model fungus, A. nidulans (see Figure 2). Functional characterisation of homologs of Aspergillus proteins such as LaeA in other fungi should lead to many more interesting discoveries. Recently detailed metabolic pathways have been constructed at complete genome
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgement
We thank the Grains Research and Development Corporation, Australia, for funds that support our research.
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