Recent advances in the genome mining of<i>Aspergillus</i>secondary metabolites (covering 2012–2018)

Romsdahl, Jillian; Wang, Clay C. C.

doi:10.1039/c9md00054b

Cited by 74 publications

(58 citation statements)

References 165 publications

(103 reference statements)

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“…These SMs play diverse ecological roles in fungal defense, communication, and virulence [13], and some of them, owing to their toxic activity, are collectively known as mycotoxins. In recent years, there have been many reviews on the production of theses type of compounds by species from the genus Aspergillus [12,[14][15][16][17][18][19][20], and specifically, A. fumigatus has the potential to produce 226 of these compounds [21]. The genes responsible for the synthesis of SMs are commonly associated with biosynthetic gene clusters [16,22,23] and the A. fumigatus genome contains between 26 and 36 putative SMs gene clusters depending on the authors [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

Guruceaga

Perez-Cuesta

Abad‐Diaz‐de‐Cerio

et al. 2019

Toxins

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Fumagillin is a mycotoxin produced, above all, by the saprophytic filamentous fungus Aspergillus fumigatus. This mold is an opportunistic pathogen that can cause invasive aspergillosis, a disease that has high mortality rates linked to it. Its ability to adapt to environmental stresses through the production of secondary metabolites, including several mycotoxins (gliotoxin, fumagillin, pseurotin A, etc.) also seem to play an important role in causing these infections. Since the discovery of the A. fumigatus fumagillin in 1949, many studies have focused on this toxin and in this review we gather all the information currently available. First of all, the structural characteristics of this mycotoxin and the different methods developed for its determination are given in detail. Then, the biosynthetic gene cluster and the metabolic pathway involved in its production and regulation are explained. The activity of fumagillin on its target, the methionine aminopeptidase type 2 (MetAP2) enzyme, and the effects of blocking this enzyme in the host are also described. Finally, the applications that this toxin and its derivatives have in different fields, such as the treatment of cancer and its microsporicidal activity in the treatment of honeybee hive infections with Nosema spp., are reviewed. Therefore, this work offers a complete review of all the information currently related to the fumagillin mycotoxin secreted by A. fumigatus, important because of its role in the fungal infection process but also because it has many other applications, notably in beekeeping, the treatment of infectious diseases, and in oncology. Key Contribution:Fumagillin is a mycotoxin produced during infections caused by A. fumigatus and in the adaptation processes of this species to multiple environmental stresses. In this review; we include detailed information on the fungal mechanisms employed in the production of this mycotoxin and those present in its regulation, how it acts on its target, and how it can be detected, all of which may be useful for diagnosis or the development of new treatments. Its usefulness in different fields is also described; because of its anti-angiogenic activity it is used to attack different types of tumors; at the same time its antibiotic activity is useful against several parasites.

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Section: Introductionmentioning

confidence: 99%

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

Guruceaga

Perez-Cuesta

Abad‐Diaz‐de‐Cerio

et al. 2019

Toxins

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“…LC-MS analysis revealed that the pheromone module proteins are required for the regulation of SM production (Figure 4). A. fumigatus is a prolific producer of SMs, most notably the immunosuppressive agent gliotoxin (Hof and Kupfahl, 2009;Romsdahl and Wang, 2019). It was evident that the deletion of any of the five pheromone module genes results in dramatic reductions in gliotoxin production in comparison to a wild type strain ( Figure 4A).…”

Section: Discussionmentioning

confidence: 99%

“…A. fumigatus growth and virulence is greatly influenced by the ability of this species to produce various bioactive compounds known as secondary metabolites (SMs), which can possess a myriad of properties. A. fumigatus has 40 predicted SM core synthase enzyme-encoding genes, 19 of which have been shown to produce downstream products (Romsdahl and Wang, 2019). The production of gliotoxin, a SM with immunosuppressive properties is a major contributor to virulence (Hof and Kupfahl, 2009) and is implicated in 96% of cases of A. fumigatus infections (Ghazaei, 2017).…”

Section: Introductionmentioning

confidence: 99%

The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus

et al. 2020

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“…The uncharacterised NRPS encoding An13g03040 as well as seven genes of this cluster expressed specifically in the 2 days IL and 2 d KMS conditions. Expression of the uncharacterised cluster An12g07060-An12g07110 [74] increased to considerable levels on late cultivation time points (Fig. 6f ).…”

Section: Novel and Known Secondary Metabolite Gene Clusters Induced Amentioning

confidence: 96%

Succession of physiological stages hallmarks the transcriptomic response of the fungus Aspergillus niger to lignocellulose

Munster

Daly

Blythe

et al. 2020

Biotechnol Biofuels

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Background: Understanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer Aspergillus niger over its life time to six substrates important for biofuel production. Results: We analysed the response of A. niger to the feedstock Miscanthus and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the Aspergillus nidulans fatty acid beta-oxidation transcriptional regulator farA, there was a reduction in expression of selected lignocellulose degradative CAZymeencoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds. Conclusion: In this study, which includes the first transcriptional response of Aspergilli to Miscanthus, we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism.

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Recent advances in the genome mining ofAspergillussecondary metabolites (covering 2012–2018)

Cited by 74 publications

References 165 publications

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

Fumagillin, a Mycotoxin of Aspergillus fumigatus: Biosynthesis, Biological Activities, Detection, and Applications

The Pheromone Module SteC-MkkB-MpkB-SteD-HamE Regulates Development, Stress Responses and Secondary Metabolism in Aspergillus fumigatus

Succession of physiological stages hallmarks the transcriptomic response of the fungus Aspergillus niger to lignocellulose

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