Molecular regulation of penicillin biosynthesis in Aspergillus (Emericella) nidulans

Brakhage, Axel A.

doi:10.1111/j.1574-6968.1997.tb10258.x

Cited by 31 publications

(7 citation statements)

References 42 publications

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“…The clustering of these three genes within the proposed MGG cluster may be functionally relevant, because yeast GPH1 is regulated by the HOG-MAP kinase pathway (71), and consequently this clustering may be indicative of a joint function in glycogen mobilization. Clustering of functionally related genes is a common feature in many eukaryotic regulatory pathways, including the nitrate assimilation cluster in Aspergillus (1,36) and the gene clusters regulating secondary metabolite biosynthesis (8,9,23). The genes of such clusters are often coregulated, not least because of their common susceptibility to changes in chromatin rearrangement (74).…”

Section: Discussionmentioning

confidence: 99%

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The G-Alpha Protein GNA3 of Hypocrea jecorina (Anamorph Trichoderma reesei ) Regulates Cellulase Gene Expression in the Presence of Light

et al. 2009

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Although the enzymes enabling Hypocrea jecorina (anamorph Trichoderma reesei) to degrade the insoluble substrate cellulose have been investigated in some detail, little is still known about the mechanism by which cellulose signals its presence to the fungus. In order to investigate the possible role of a G-protein/cyclic AMP signaling pathway, the gene encoding GNA3, which belongs to the adenylate cyclase-activating class III of G-alpha subunits, was cloned. gna3 is clustered in tandem with the mitogen-activated protein kinase gene tmk3 and the glycogen phosphorylase gene gph1. The gna3 transcript is upregulated in the presence of light and is almost absent in the dark. A strain bearing a constitutively activated version of GNA3 (gna3QL) exhibits strongly increased cellulase transcription in the presence of the inducer cellulose and in the presence of light, whereas a gna3 antisense strain showed delayed cellulase transcription under this condition. However, the gna3QL mutant strain was unable to form cellulases in the absence of cellulose. The necessity of light for stimulation of cellulase transcription by GNA3 could not be overcome in a mutant which expressed gna3 under control of the constitutive gpd1 promoter also in darkness. We conclude that the previously reported stimulation of cellulase gene transcription by light, but not the direct transmission of the cellulose signal, involves the function and activation of GNA3. The upregulation of gna3 by light is influenced by the light modulator ENVOY, but GNA3 itself has no effect on transcription of the light regulator genes blr1, blr2, and env1. Our data for the first time imply an involvement of a G-alpha subunit in a light-dependent signaling event in fungi.

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Section: Discussionmentioning

confidence: 99%

“…VOL. 8,2009 G-PROTEIN-MEDIATED CELLULASE REGULATION 413 on July 4, 2020 by guest http://ec.asm.org/ different darkness-and light-related functions of ENVOY (62). Stimulation of gna3 gene expression on glycerol occurred within 30 min of illumination and reached a peak after 60 min (Fig.…”

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confidence: 96%

The G-Alpha Protein GNA3 of Hypocrea jecorina (Anamorph Trichoderma reesei ) Regulates Cellulase Gene Expression in the Presence of Light

et al. 2009

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“…For the PN cluster, we examined two of the three genes in the cluster, ipnA and penDE (aatA), encoding an isopenicillin N synthetase and an isopenicillin N acyltransferase, respectively. Both genes are essential for PN production (7).…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, this group of enzymes was chosen to study the effects of histone deacetylation on small-molecule production. We examined the effects of HDAC loss on the three bestcharacterized SM clusters in A. nidulans, the sterigmatocystin (ST) (a member of the carcinogenic and insecticidal aflatoxins) cluster (8), the penicillin (PN) (an antibiotic) cluster (7), and the terraquinone A (TR) (an antitumor agent) cluster (6). All three clusters are positively regulated by LaeA (3,4).…”

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confidence: 99%

Histone Deacetylase Activity Regulates Chemical Diversity in Aspergillus

et al. 2007

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Bioactive small molecules are critical in Aspergillus species during their development and interaction with other organisms. Genes dedicated to their production are encoded in clusters that can be located throughout the genome. We show that deletion of hdaA, encoding an Aspergillus nidulans histone deacetylase (HDAC), causes transcriptional activation of two telomere-proximal gene clusters-and subsequent increased levels of the corresponding molecules (toxin and antibiotic)-but not of a telomere-distal cluster. Introduction of two additional HDAC mutant alleles in a ⌬hdaA background had minimal effects on expression of the two HdaA-regulated clusters. Treatment of other fungal genera with HDAC inhibitors resulted in overproduction of several metabolites, suggesting a conserved mechanism of HDAC repression of some secondary-metabolite gene clusters. Chromatin regulation of small-molecule gene clusters may enable filamentous fungi to successfully exploit environmental resources by modifying chemical diversity.A distinguishing characteristic of filamentous fungi is their ability to produce a wide variety of small molecules that aid in their survival and pathogenicity. These include compounds, such as pigments, that play a role in virulence and protect the fungus from environmental damage, as well as toxins that kill host tissues or hinder competition from other organisms. These secondary metabolites (SM) (27) can also impact humans in both beneficial and detrimental ways. Many widely used pharmaceuticals are natural products of fungi, as are some of the most potent carcinogens yet identified. Genetic studies, augmented by analysis of whole genome sequences, have revealed that most fungal SM biosynthetic genes are found in compact clusters functioning as individual genetic loci (27). The genus Aspergillus, whose members include toxinproducing pathogens (Aspergillus flavus and A. fumigatus) and pharmaceutical-producing species (A. nidulans and A. terreus), is renowned for prodigious metabolite production and serves as the model for natural-product exploration. Detailed comparison of the genomes of several aspergilli indicates a genomic landscape in which the greatest diversity between species is represented in these SM clusters (28).There has been considerable debate as to the role that gene clustering plays in the secondary metabolism of fungi. Such gene arrangement must be advantageous to the fungus; if natural selection did not favor clustering, one would assume that processes such as gene translocation and unequal crossing over would have caused dispersal over evolutionary history. Support for horizontal transfer from prokaryotes, in which genes are often arranged into operons, exists for the penicillin biosynthetic cluster (9) but not for other fungal clusters. A prokaryotic gene transfer hypothesis is weakened by the fact that fungal SM genes often contain introns and employ codon usage typical of other fungal genes. Another hypothesis holds that clustering provides a selective advantage to the cluster itself i...

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“…Fewer fungal genes encoding NRPS have been fully sequenced and characterized experimentally. These genes include acvA from Aspergillus nidulans and Penicillium chrysogenum, which controls the production of the precursor of b-lactam antibiotics such as penicillin (Brakhage, 1997); simA from Tolypocladium inflatum, which controls the production of cyclosporin A and is used as an immunosuppressive drug in organ transplant surgery (Weber et al, 1994); and sidA, which controls production of the siderophores N9,N9,N999-triacetylfusarinine C (TAF) and ferricrocin, which are virulence factors in Aspergillus fumigatus (Hissen et al, 2005). To date, the genomic sequences of fungi appear to have the potential for faster discovery of novel NRPS genes.…”

Section: Introductionmentioning

confidence: 99%

Identification of the nonribosomal peptide synthetase gene responsible for bassianolide synthesis in wood-decaying fungus Xylaria sp. BCC1067

et al. 2008

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Molecular regulation of penicillin biosynthesis in Aspergillus (Emericella) nidulans

Cited by 31 publications

References 42 publications

The G-Alpha Protein GNA3 of Hypocrea jecorina (Anamorph Trichoderma reesei ) Regulates Cellulase Gene Expression in the Presence of Light

The G-Alpha Protein GNA3 of Hypocrea jecorina (Anamorph Trichoderma reesei ) Regulates Cellulase Gene Expression in the Presence of Light

Histone Deacetylase Activity Regulates Chemical Diversity in Aspergillus

Identification of the nonribosomal peptide synthetase gene responsible for bassianolide synthesis in wood-decaying fungus Xylaria sp. BCC1067

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