A survey of nonribosomal peptide synthetase (NRPS) genes in Aspergillus nidulans

Döhren, Hans von

doi:10.1016/j.fgb.2008.08.008

Cited by 83 publications

(72 citation statements)

References 46 publications

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“…Ten genes belong to this first group, 5 being upregulated at the early AD and 5 downregulated. In this group are the PKS-coding genes An2032 (also known as pkhA), related to benzaldehyde derivative biosynthesis, An6791, An8910, An9005, and An12331 (ϭ An7838), the NRPS-coding genes An2064, An5318, and An6236 (also known as sidD), related to fusarininetype siderophore biosynthesis, and An9129, and the hybrid PKS-NRPS-coding gene An8412 (also known as apdA), involved in aspyridone synthesis (74,(84)(85)(86)(87).…”

Section: Resultsmentioning

confidence: 99%

“…We included three more PKS-or NRPS-coding genes in this analysis, since although they were not significantly regulated, they defined genomic regions where contiguous genes were significantly regulated (see black squares in Fig. 5) (74,84): An2035 (also known as pkhB), located in the same metabolic cluster as An2032 (pkhA) (see above), An3230 (also known as pkfA), involved in orsellinaldehyde derivative synthesis, and the NRPS gene An11820 (ϭ An9291). Based on these criteria, we focused on seven clusters in which at least three genes were significantly regulated, one of them being the PKS-or NRPS-coding gene or not (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Transcriptional Changes in the Transition from Vegetative Cells to Asexual Development in the Model Fungus Aspergillus nidulans

et al. 2013

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cMorphogenesis encompasses programmed changes in gene expression that lead to the development of specialized cell types. In the model fungus Aspergillus nidulans, asexual development involves the formation of characteristic cell types, collectively known as the conidiophore. With the aim of determining the transcriptional changes that occur upon induction of asexual development, we have applied massive mRNA sequencing to compare the expression pattern of 19-h-old submerged vegetative cells (hyphae) with that of similar hyphae after exposure to the air for 5 h. We found that the expression of 2,222 (20.3%) of the predicted 10,943 A. nidulans transcripts was significantly modified after air exposure, 2,035 being downregulated and 187 upregulated. The activation during this transition of genes that belong specifically to the asexual developmental pathway was confirmed. Another remarkable quantitative change occurred in the expression of genes involved in carbon or nitrogen primary metabolism. Genes participating in polar growth or sexual development were transcriptionally repressed, as were those belonging to the HogA/SakA stress response mitogen-activated protein (MAP) kinase pathway. We also identified significant expression changes in several genes purportedly involved in redox balance, transmembrane transport, secondary metabolite production, or transcriptional regulation, mainly binuclear-zinc cluster transcription factors. Genes coding for these four activities were usually grouped in metabolic clusters, which may bring regulatory implications for the induction of asexual development. These results provide a blueprint for further stage-specific gene expression studies during conidiophore development.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Transcriptional Changes in the Transition from Vegetative Cells to Asexual Development in the Model Fungus Aspergillus nidulans

et al. 2013

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“…The latter conclusion was based on the presence of genes coding for thiotemplate assembly lines, such as polyketide synthases (PKSs) (3) and nonribosomal peptide synthetases (NRPSs) (4) in various microorganisms. For example, the important model fungus Aspergillus nidulans harbors 28 putative PKS and 24 NRPS gene clusters (4), giving this fungus the potential to produce at least 52 different secondary metabolites. Recent data further complicate a serious estimation because communication occurs between gene clusters, which could potentially lead to even more compounds (5).…”

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confidence: 99%

Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation

Nützmann

Reyes-Domínguez

Scherlach

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

312

270

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Sequence analyses of fungal genomes have revealed that the potential of fungi to produce secondary metabolites is greatly underestimated. In fact, most gene clusters coding for the biosynthesis of antibiotics, toxins, or pigments are silent under standard laboratory conditions. Hence, it is one of the major challenges in microbiology to uncover the mechanisms required for pathway activation. Recently, we discovered that intimate physical interaction of the important model fungus Aspergillus nidulans with the soil-dwelling bacterium Streptomyces rapamycinicus specifically activated silent fungal secondary metabolism genes, resulting in the production of the archetypal polyketide orsellinic acid and its derivatives. Here, we report that the streptomycete triggers modification of fungal histones. Deletion analysis of 36 of 40 acetyltransferases, including histone acetyltransferases (HATs) of A. nidulans, demonstrated that the Saga/Ada complex containing the HAT GcnE and the AdaB protein is required for induction of the orsellinic acid gene cluster by the bacterium. We also showed that Saga/Ada plays a major role for specific induction of other biosynthesis gene clusters, such as sterigmatocystin, terrequinone, and penicillin. Chromatin immunoprecipitation showed that the Saga/Ada-dependent increase of histone 3 acetylation at lysine 9 and 14 occurs during interaction of fungus and bacterium. Furthermore, the production of secondary metabolites in A. nidulans is accompanied by a global increase in H3K14 acetylation. Increased H3K9 acetylation, however, was only found within gene clusters. This report provides previously undescribed evidence of Saga/Ada dependent histone acetylation triggered by prokaryotes.

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“…4 Mining the genome of Aspergillus nidulans for putative biosynthesis gene clusters revealed biosynthetic abilities for the production of up to 28 polyketides and 24 nonribosomally synthesized peptides. 5,6 However, this abundance of gene clusters clearly outnumbers the known secondary metabolites of this fungus. To gain access to this untapped reservoir of potentially bioactive natural products, various strategies to induce the expression of silent genes have been developed.…”

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confidence: 98%

“…Although a couple of isoindole derivatives have been isolated from fungal sources, the production of such metabolites has not yet been reported for A. nidulans. Zinnimidine (3) and porritoxin (4) were isolated from Alternaria porri, 17-19 6-hydroxy-4-methoxy-5-methylphthalimidine (5) from cultures of Aspergillus silvaticus 20 and duricaulic acid (6) from Aspergillus duricaulis. 21 Several isoindoles are also produced by Stachybotrys spp.…”

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confidence: 99%

Aspernidine A and B, prenylated isoindolinone alkaloids from the model fungus Aspergillus nidulans

et al. 2010

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Filamentous fungi produce a multitude of bioactive natural products, which cover a broad range of useful pharmaceutical activities. Many of these compounds were discovered by traditional natural product screening approaches and have found various applications in modern medicine. 1,2 Through recent whole-genome sequencing projects, however, we become increasingly aware that the biosynthetic potential of microorganisms is much higher than expected. 3 In many cases, the number of putative biosynthetic genes of fungi and bacteria is not reflected by the metabolic profile observed under laboratory culture conditions. Several gene loci encoding diverse metabolic pathways seem to lack expression in the absence of particular physical or chemical stimuli. 4 Mining the genome of Aspergillus nidulans for putative biosynthesis gene clusters revealed biosynthetic abilities for the production of up to 28 polyketides and 24 nonribosomally synthesized peptides. 5,6 However, this abundance of gene clusters clearly outnumbers the known secondary metabolites of this fungus. To gain access to this untapped reservoir of potentially bioactive natural products, various strategies to induce the expression of silent genes have been developed. 4,7 Important recent examples involve the ectopic expression of a regulatory gene, 8 the induction of a transcription activator by promotor exchange, 9 as well as modulation of the epigenetic regulation of biosynthetic genes at the chromatin level. [10][11][12][13] Furthermore, it was shown that the intimate contact between A. nidulans and a soil-dwelling actinomycete may lead to the specific induction of a cryptic polyketide gene cluster. 14 These strategies resulted in the discovery of a set of novel secondary metabolites, which could not be located by classical screening methods. Another option often preceding genomic approaches is the systematic investigation of the microbial secondary metabolome under various growth conditions. Since the early days of fermentations, it is known that the choice of the cultivation parameters is critical to the number and type of secondary metabolites produced by microorganisms. 4 Thus, the formation of cryptic natural products can up to a certain extent be triggered by a systematic variation of standard fermentation parameters to increase the number of secondary compounds produced in the bacterial or fungal culture. 15,16 On the basis of the assumption that changing environmental conditions can shift the metabolic profile of an organism, we systematically varied the cultivation parameters to reinvestigate the metabolome of A. nidulans. In this study, we report the discovery of two new isoindole alkaloids, aspernidine A (1) and B (2), as an addition to the metabolic data of this important model fungus (Figure 1a). An A. nidulans extract library was prepared by adjusting 45 different culture conditions (variation of culture media, cultivation period, temperature and oxygen supply) and the metabolic profiles were screened by HPLC-DAD-MS. Investigation of the cultur...

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A survey of nonribosomal peptide synthetase (NRPS) genes in Aspergillus nidulans

Cited by 83 publications

References 46 publications

Transcriptional Changes in the Transition from Vegetative Cells to Asexual Development in the Model Fungus Aspergillus nidulans

Transcriptional Changes in the Transition from Vegetative Cells to Asexual Development in the Model Fungus Aspergillus nidulans

Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation

Aspernidine A and B, prenylated isoindolinone alkaloids from the model fungus Aspergillus nidulans

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