Genomic analysis of the secretion stress response in the enzyme-producing cell factory Aspergillus niger

Guillemette, Thomas; Peij, Noël N. M. E. van; Goosen, T.; Lanthaler, Karin; Robson, Geoffrey D.; Hondel, Cees A. M. J. J. van den; Stam, H.; Archer, David B.

doi:10.1186/1471-2164-8-158

Cited by 148 publications

(174 citation statements)

References 54 publications

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“…These proteases (68%) also contained a signal peptide indicating a potential extracellular role. Studies on protease activity in A. niger are mainly focused in exploiting its naturally high secretion capacity in biotechnology by manipulating A. niger strains that are more efficient in recombinant protein production [19]. Extracellular proteases generally play a role in the breakdown of large polypeptides into smaller molecules for absorption by the cell [53].…”

Section: Discussionmentioning

confidence: 99%

“…However, protein overexpression in A. niger can be limited by redox stress and the UPR [17], and we speculated if revelation of the mechanism of GT sensitivity in A. niger could provide new insight into factors which negatively affect [18] protein expression. Studies of the transcriptional and translational response to stress agents (DTT and tunicamycin) in A. niger have been carried out in order to elucidate ways of overcoming this barrier to successful protein expression [13,19].…”

Section: Introductionmentioning

confidence: 99%

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Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger

Manzanares-Miralles

Sarikaya-Bayram

Smith

et al. 2016

Journal of Proteomics

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a b s t r a c t a r t i c l e i n f oGliotoxin (GT) is a redox-active metabolite, produced by Aspergillus fumigatus, which inhibits the growth of other fungi. Here we demonstrate how Aspergillus niger responds to GT exposure. Quantitative proteomics revealed that GT dysregulated the abundance of 378 proteins including those involved in methionine metabolism and induced de novo abundance of two S-adenosylmethionine (SAM)-dependent methyltransferases. Increased abundance of enzymes S-adenosylhomocysteinase (p = 0.0018) required for homocysteine generation from S-adenosylhomocysteine (SAH), and spermidine synthase (p = 0.0068), involved in the recycling of Met, was observed. Analysis of Met-related metabolites revealed significant increases in the levels of Met and adenosine, in correlation with proteomic data. Methyltransferase MT-II is responsible for bisthiobis(methylthio)gliotoxin (BmGT) formation, deletion of MT-II abolished BmGT formation and led to increased GT sensitivity in A. niger. Proteomic analysis also revealed that GT exposure also significantly (p b 0.05) increased hydrolytic enzyme abundance, including glycoside hydrolases (n = 22) and peptidases (n = 16). We reveal that in an attempt to protect against the detrimental affects of GT, methyltransferase-mediated GT thiomethylation alters cellular pathways involving Met and SAM, with consequential dysregulation of hydrolytic enzyme abundance in A. niger. Thus, it provides new opportunities to exploit the response of GT-naïve fungi to GT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger

Manzanares-Miralles

Sarikaya-Bayram

Smith

et al. 2016

Journal of Proteomics

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“…For example, under conditions where A. niger [31] or T. reesei [135] were transferred from glucose-grown conditions to wheat straw, where the secretion of CAZy enzymes is induced, there was no clear impact on the transcript levels of selected UPR marker genes such as hacA/1, bipA/1 or pdiA/1, although the UPR involves transcript level changes to several hundreds of genes, e.g. in A. niger [145]. The apparent lack of induction of the UPR was presumably because the CAZymes secreted were native proteins that the fungi naturally secrete well and that the enzyme levels secreted did not cause undue load on the system at the time-points studied.…”

Section: Endoplasmic Reticulum (Er) Stressmentioning

confidence: 99%

Transcriptional Regulation and Responses in Filamentous Fungi Exposed to Lignocellulose

2015

Mycology: Current and Future Developments

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Biofuels derived from lignocellulose are attractive alternative fuels but their production suffers from a costly and inefficient saccharification step that uses fungal enzymes. One route to improve this efficiency is to understand better the transcriptional regulation and responses of filamentous fungi to lignocellulose. Sensing and initial contact of the fungus with lignocellulose is an important aspect. Differences and similarities in the responses of fungi to different lignocellulosic substrates can partly be explained with existing understanding of several key regulators and their mode of action, as will be demonstrated for Trichoderma reesei, Neurospora crassa and Aspergillus spp. The regulation of genes encoding Carbohydrate Active enZymes (CAZymes) is influenced by the presence of carbohydrate monomers and short oligosaccharides, as well as the external stimuli of pH and light. We explore several important aspects of the response to lignocellulose that are not related to genes encoding CAZymes, namely the regulation of transporters, accessory proteins and stress responses. The regulation of gene expression is examined from the perspective of mixed cultures and models are presented for the nature of the transcriptional basis for any beneficial effects of such mixed cultures. Various applications in biofuel technology are based on manipulating transcriptional regulation and learning from fungal responses to lignocelluloses. Here we critically access the application of fungal transcriptional responses to industrial saccharification reactions. As part of this chapter, selected regulatory mechanisms are also explored in more detail.

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“…In contrast, yields in the grams-per-liter range are only obtained with a few yeast strains (Pichia, Hansenula) used for extracellular protein production 71,72) . Filamentous fungi grow by extension of hyphal tips 15,66) involving the actin cytoskeleton, signal transduction pathways, cell wall formation, membrane biosynthesis and the secretion pathway 15,22,52,53,55) . In particular, this hyphal growth phenotype of filamentous fungi, which is not found in either S. cerevisiae or in higher eukaryotic organisms, may contribute to the higher protein secretion capacity of filamentous fungi compared to S. cerevisiae.…”

Section: Secretion Of Proteins and Growth Phenotype Of Filamentous Fungimentioning

confidence: 99%

Scientific Advances with Aspergillus Species that Are Used for Food and Biotech Applications

Biesebeke

Record²

2008

Microb. Environ.

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Yeast and filamentous fungi have been used for centuries in diverse biotechnological processes. Fungal fermentation technology is traditionally used in relation to food production, such as for bread, beer, cheese, sake and soy sauce. Last century, the industrial application of yeast and filamentous fungi expanded rapidly, with excellent examples such as purified enzymes and secondary metabolites (e.g. antibiotics), which are used in a wide range of food as well as nonfood industries. Research on protein and/or metabolite secretion by fungal species has focused on identifying bottlenecks in (post-) transcriptional regulation of protein production, metabolic rerouting, morphology and the transit of proteins through the secretion pathway. In past years, genome sequencing of some fungi (e.g. Aspergillus oryzae, Aspergillus niger) has been completed. The available genome sequences have enabled identification of genes and functionally important regions of the genome. This has directed research to focus on a post-genomics era in which transcriptomics, proteomics and metabolomics methodologies will help to explore the scientific relevance and industrial application of fungal genome sequences.

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Genomic analysis of the secretion stress response in the enzyme-producing cell factory Aspergillus niger

Cited by 148 publications

References 54 publications

Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger

Quantitative proteomics reveals the mechanism and consequence of gliotoxin-mediated dysregulation of the methionine cycle in Aspergillus niger

Transcriptional Regulation and Responses in Filamentous Fungi Exposed to Lignocellulose

Scientific Advances with Aspergillus Species that Are Used for Food and Biotech Applications

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