Journal articles: 'Fungal secondary metabolism'

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Brakhage, Axel A. "Regulation of fungal secondary metabolism." Nature Reviews Microbiology 11, no. 1 (November 26, 2012): 21–32. http://dx.doi.org/10.1038/nrmicro2916.

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Khalil, Zeinab G., Pabasara Kalansuriya, and Robert J. Capon. "Lipopolysaccharide (LPS) stimulation of fungal secondary metabolism." Mycology 5, no. 3 (July 3, 2014): 168–78. http://dx.doi.org/10.1080/21501203.2014.930530.

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Calvo, Ana M., Richard A. Wilson, Jin Woo Bok, and Nancy P. Keller. "Relationship between Secondary Metabolism and Fungal Development." Microbiology and Molecular Biology Reviews 66, no. 3 (September 2002): 447–59. http://dx.doi.org/10.1128/mmbr.66.3.447-459.2002.

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SUMMARY Filamentous fungi are unique organisms—rivaled only by actinomycetes and plants—in producing a wide range of natural products called secondary metabolites. These compounds are very diverse in structure and perform functions that are not always known. However, most secondary metabolites are produced after the fungus has completed its initial growth phase and is beginning a stage of development represented by the formation of spores. In this review, we describe secondary metabolites produced by fungi that act as sporogenic factors to influence fungal development, are required for spore viability, or are produced at a time in the life cycle that coincides with development. We describe environmental and genetic factors that can influence the production of secondary metabolites. In the case of the filamentous fungus Aspergillus nidulans, we review the only described work that genetically links the sporulation of this fungus to the production of the mycotoxin sterigmatocystin through a shared G-protein signaling pathway.

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Keller, Nancy P., Geoffrey Turner, and Joan W. Bennett. "Fungal secondary metabolism — from biochemistry to genomics." Nature Reviews Microbiology 3, no. 12 (December 2005): 937–47. http://dx.doi.org/10.1038/nrmicro1286.

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Yin, Wenbing, and Nancy P. Keller. "Transcriptional regulatory elements in fungal secondary metabolism." Journal of Microbiology 49, no. 3 (June 2011): 329–39. http://dx.doi.org/10.1007/s12275-011-1009-1.

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Bennett, J. W. "From molecular genetics and secondary metabolism to molecular metabolites and secondary genetics." Canadian Journal of Botany 73, S1 (December 31, 1995): 917–24. http://dx.doi.org/10.1139/b95-339.

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Secondary metabolites constitute a huge array of low molecular weight natural products that cannot be easily defined. Largely produced by bacteria, fungi, and green plants, they tend to be synthesized after active growth has ceased, in families of similar compounds, often at the same time as species-specific morphological characters become apparent. Although, in many cases, the function that the secondary metabolite performs in the producing organism is unknown, the bioactivity of these compounds has been exploited since prehistoric times as drugs, poisons, food flavoring agents, and so forth. In fungi, the polyketide family is the largest known group of secondary metabolite compounds. Polyketides are synthesized from acetate by a mechanism analogous to fatty acid biosynthesis but involving changes in oxidation level and stereochemistry during the chain-elongation process. The fungal polyketide biosynthetic pathways for aflatoxin and patulin have emerged as model systems. The use of blocked mutants has been an essential part of the research approach for both pathways. Molecular methods of studying fungal secondary metabolites were first used with penicillin and cephalosporin, both of which are amino acid derived. Most of the basic molecular work on polyketides was done with streptomycete-derived compounds; however, enough fungal data are now available to compare fungal and streptomycete polyketide synthases, as well as to map the genes involved in a number of polyketide pathways from both groups. The traditional dogma, derived from classical genetics, that genes for fungal pathways are unlinked, has been overturned. In addition, cloning of structural genes facilitates the formation of hybrid molecules, and we are on the brink of understanding certain regulatory functions. Key words: fungal metabolism, secondary metabolism, polyketide, β-lactam, product discovery.

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Calcott, Mark J., David F. Ackerley, Allison Knight, Robert A. Keyzers, and Jeremy G. Owen. "Secondary metabolism in the lichen symbiosis." Chemical Society Reviews 47, no. 5 (2018): 1730–60. http://dx.doi.org/10.1039/c7cs00431a.

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Lichens, which are defined by a symbiosis between a mycobiont (fungal partner) and a photobiont (photoautotrophic partner), are in fact complex assemblages of microorganisms that constitute a largely untapped source of bioactive secondary metabolites.

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Fox, Ellen M., and Barbara J. Howlett. "Secondary metabolism: regulation and role in fungal biology." Current Opinion in Microbiology 11, no. 6 (December 2008): 481–87. http://dx.doi.org/10.1016/j.mib.2008.10.007.

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Keller, Nancy P. "Fungal secondary metabolism: regulation, function and drug discovery." Nature Reviews Microbiology 17, no. 3 (December 10, 2018): 167–80. http://dx.doi.org/10.1038/s41579-018-0121-1.

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Chanda, A., L. V. Roze, S. Kang, K. A. Artymovich, G. R. Hicks, N. V. Raikhel, A. M. Calvo, and J. E. Linz. "A key role for vesicles in fungal secondary metabolism." Proceedings of the National Academy of Sciences 106, no. 46 (November 4, 2009): 19533–38. http://dx.doi.org/10.1073/pnas.0907416106.

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Scharf, Daniel H., and Axel A. Brakhage. "Engineering fungal secondary metabolism: A roadmap to novel compounds." Journal of Biotechnology 163, no. 2 (January 2013): 179–83. http://dx.doi.org/10.1016/j.jbiotec.2012.06.027.

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Kawauchi, Moriyuki, Mika Nishiura, and Kazuhiro Iwashita. "Fungus-Specific Sirtuin HstD Coordinates Secondary Metabolism and Development through Control of LaeA." Eukaryotic Cell 12, no. 8 (May 31, 2013): 1087–96. http://dx.doi.org/10.1128/ec.00003-13.

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ABSTRACT The sirtuins are members of the NAD + -dependent histone deacetylase family that contribute to various cellular functions that affect aging, disease, and cancer development in metazoans. However, the physiological roles of the fungus-specific sirtuin family are still poorly understood. Here, we determined a novel function of the fungus-specific sirtuin HstD/ Aspergillus oryzae Hst4 (AoHst4), which is a homolog of Hst4 in A. oryzae yeast. The deletion of all histone deacetylases in A. oryzae demonstrated that the fungus-specific sirtuin HstD/AoHst4 is required for the coordination of fungal development and secondary metabolite production. We also show that the expression of the laeA gene, which is the most studied fungus-specific coordinator for the regulation of secondary metabolism and fungal development, was induced in a Δ hstD strain. Genetic interaction analysis of hstD / Aohst4 and laeA clearly indicated that HstD/AoHst4 works upstream of LaeA to coordinate secondary metabolism and fungal development. The hstD/Aohst4 and laeA genes are fungus specific but conserved in the vast family of filamentous fungi. Thus, we conclude that the fungus-specific sirtuin HstD/AoHst4 coordinates fungal development and secondary metabolism via the regulation of LaeA in filamentous fungi.

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Chiang, Yi-Ming, Kuan-Han Lee, James F. Sanchez, Nancy P. Keller, and Clay C. C. Wang. "Unlocking Fungal Cryptic Natural Products." Natural Product Communications 4, no. 11 (November 2009): 1934578X0900401. http://dx.doi.org/10.1177/1934578x0900401113.

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Recent published sequencing of fungal genomes has revealed that these microorganisms have a surprisingly large number of secondary metabolite pathways that can serve as potential sources for new and useful natural products. Most of the secondary metabolites and their biosynthesis pathways are currently unknown, possibly because they are produced in very small amounts and are thus difficult to detect or are produced only under specific conditions. Elucidating these fungal metabolites will require new molecular genetic tools, better understanding of the regulation of secondary metabolism, and state of the art analytical methods. This review describes recent strategies to mine the cryptic natural products and their biosynthetic pathways in fungi.

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Derntl, Christian, Bernhard Kluger, Christoph Bueschl, Rainer Schuhmacher, Robert L. Mach, and Astrid R. Mach-Aigner. "Transcription factor Xpp1 is a switch between primary and secondary fungal metabolism." Proceedings of the National Academy of Sciences 114, no. 4 (January 10, 2017): E560—E569. http://dx.doi.org/10.1073/pnas.1609348114.

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Fungi can produce a wide range of chemical compounds via secondary metabolism. These compounds are of major interest because of their (potential) application in medicine and biotechnology and as a potential source for new therapeutic agents and drug leads. However, under laboratory conditions, most secondary metabolism genes remain silent. This circumstance is an obstacle for the production of known metabolites and the discovery of new secondary metabolites. In this study, we describe the dual role of the transcription factor Xylanase promoter binding protein 1 (Xpp1) in the regulation of both primary and secondary metabolism of Trichoderma reesei. Xpp1 was previously described as a repressor of xylanases. Here, we provide data from an RNA-sequencing analysis suggesting that Xpp1 is an activator of primary metabolism. This finding is supported by our results from a Biolog assay determining the carbon source assimilation behavior of an xpp1 deletion strain. Furthermore, the role of Xpp1 as a repressor of secondary metabolism is shown by gene expression analyses of polyketide synthases and the determination of the secondary metabolites of xpp1 deletion and overexpression strains using an untargeted metabolomics approach. The deletion of Xpp1 resulted in the enhanced secretion of secondary metabolites in terms of diversity and quantity. Homologs of Xpp1 are found among a broad range of fungi, including the biocontrol agent Trichoderma atroviride, the plant pathogens Fusarium graminearum and Colletotrichum graminicola, the model organism Neurospora crassa, the human pathogen Sporothrix schenckii, and the ergot fungus Claviceps purpurea.

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Gu, Qin, Zhenzhong Wang, Xiao Sun, Tiantian Ji, Hai Huang, Yang Yang, Hao Zhang, et al. "FvSet2 regulates fungal growth, pathogenicity, and secondary metabolism in Fusarium verticillioides." Fungal Genetics and Biology 107 (October 2017): 24–30. http://dx.doi.org/10.1016/j.fgb.2017.07.007.

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Claesson, M., and G. Schneider. "The structure of a novel bifunctional dehydratase/isomerase from fungal secondary metabolism." Acta Crystallographica Section A Foundations of Crystallography 67, a1 (August 22, 2011): C794. http://dx.doi.org/10.1107/s010876731107989x.

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Kim, H., H. Son, and Y. W. Lee. "Effects of light on secondary metabolism and fungal development of Fusarium graminearum." Journal of Applied Microbiology 116, no. 2 (November 19, 2013): 380–89. http://dx.doi.org/10.1111/jam.12381.

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Becker, Kevin, and Marc Stadler. "Recent progress in biodiversity research on the Xylariales and their secondary metabolism." Journal of Antibiotics 74, no. 1 (October 23, 2020): 1–23. http://dx.doi.org/10.1038/s41429-020-00376-0.

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AbstractThe families Xylariaceae and Hypoxylaceae (Xylariales, Ascomycota) represent one of the most prolific lineages of secondary metabolite producers. Like many other fungal taxa, they exhibit their highest diversity in the tropics. The stromata as well as the mycelial cultures of these fungi (the latter of which are frequently being isolated as endophytes of seed plants) have given rise to the discovery of many unprecedented secondary metabolites. Some of those served as lead compounds for development of pharmaceuticals and agrochemicals. Recently, the endophytic Xylariales have also come in the focus of biological control, since some of their species show strong antagonistic effects against fungal and other pathogens. New compounds, including volatiles as well as nonvolatiles, are steadily being discovered from these ascomycetes, and polythetic taxonomy now allows for elucidation of the life cycle of the endophytes for the first time. Moreover, recently high-quality genome sequences of some strains have become available, which facilitates phylogenomic studies as well as the elucidation of the biosynthetic gene clusters (BGC) as a starting point for synthetic biotechnology approaches. In this review, we summarize recent findings, focusing on the publications of the past 3 years.

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Shaaban, Mona I., Jin Woo Bok, Carrie Lauer, and Nancy P. Keller. "Suppressor Mutagenesis Identifies a Velvet Complex Remediator of Aspergillus nidulans Secondary Metabolism." Eukaryotic Cell 9, no. 12 (October 8, 2010): 1816–24. http://dx.doi.org/10.1128/ec.00189-10.

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ABSTRACT Fungal secondary metabolites (SM) are bioactive compounds that are important in fungal ecology and, moreover, both harmful and useful in human endeavors (e.g., as toxins and pharmaceuticals). Recently a nuclear heterocomplex termed the Velvet complex, characterized in the model ascomycete Aspergillus nidulans, was found to be critical for SM production. Deletion of two members of the Velvet complex, laeA and veA, results in near loss of SM and defective sexual spore production in A. nidulans and other species. Using a multicopy-suppressor genetics approach, we have isolated an Aspergillus nidulans gene named rsm A (remediation of secondary metabolism) based upon its ability to remediate secondary metabolism in ΔlaeA and ΔveA backgrounds. Overexpression of rsmA (OE::rsmA) restores production of sterigmatocystin (ST) (a carcinogenic SM) via transcriptional activation of ST biosynthetic genes. However, defects in sexual reproduction in either ΔlaeA or ΔveA strains cannot be overcome by OE::rsmA. An intact Velvet complex coupled with an OE::rsmA allele increases SM many fold over the wild-type level, but loss of rsmA does not decrease SM. RsmA encodes a putative bZIP basic leucine zipper-type transcription factor.

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Bayram, O., S. Krappmann, M. Ni, J. W. Bok, K. Helmstaedt, O. Valerius, S. Braus-Stromeyer, et al. "VelB/VeA/LaeA Complex Coordinates Light Signal with Fungal Development and Secondary Metabolism." Science 320, no. 5882 (June 13, 2008): 1504–6. http://dx.doi.org/10.1126/science.1155888.

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Bok, Jin Woo, and Nancy P. Keller. "LaeA, a Regulator of Secondary Metabolism in Aspergillus spp." Eukaryotic Cell 3, no. 2 (April 2004): 527–35. http://dx.doi.org/10.1128/ec.3.2.527-535.2004.

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ABSTRACT Secondary metabolites, or biochemical indicators of fungal development, are of intense interest to humankind due to their pharmaceutical and/or toxic properties. We present here a novel Aspergillus nuclear protein, LaeA, as a global regulator of secondary metabolism in this genus. Deletion of laeA (ΔlaeA) blocks the expression of metabolic gene clusters, including the sterigmatocystin (carcinogen), penicillin (antibiotic), and lovastatin (antihypercholesterolemic agent) gene clusters. Conversely, overexpression of laeA triggers increased penicillin and lovastatin gene transcription and subsequent product formation. laeA expression is negatively regulated by AflR, a sterigmatocystin Zn2Cys6 transcription factor, in a unique feedback loop, as well as by two signal transduction elements, protein kinase A and RasA. Although these last two proteins also negatively regulate sporulation, ΔlaeA strains show little difference in spore production compared to the wild type, indicating that the primary role of LaeA is to regulate metabolic gene clusters.

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Nützmann, Hans-Wilhelm, Juliane Fischer, Kirstin Scherlach, Christian Hertweck, and Axel A. Brakhage. "Distinct Amino Acids of Histone H3 Control Secondary Metabolism in Aspergillus nidulans." Applied and Environmental Microbiology 79, no. 19 (July 26, 2013): 6102–9. http://dx.doi.org/10.1128/aem.01578-13.

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ABSTRACTChromatin remodelling events play an important role in the secondary metabolism of filamentous fungi. Previously, we showed that a bacterium,Streptomyces rapamycinicus, is able to reprogram the histone-modifying Spt-Ada-Gcn5-acetyltransferase/ADA (SAGA/ADA) complex of the model fungusAspergillus nidulans. Consequently, the histone H3 amino acids lysine 9 and lysine 14 at distinct secondary metabolism genes were specifically acetylated during the bacterial fungal interaction, which, furthermore, was associated with the activation of the otherwise silent orsellinic acid gene cluster. To investigate the importance of the histone modifications for distinct gene expression profiles in fungal secondary metabolism, we exchanged several amino acids of histone H3 ofA. nidulans. These amino acids included lysine residues 9, 14, 18, and 23 as well as serine 10 and threonine 11. Lysine residues were replaced by arginine or glutamine residues, and serine/threonine residues were replaced by alanine. All generated mutant strains were viable, allowing direct analysis of the consequences of missing posttranslational histone modifications. In the mutant strains, major changes in the expression patterns at both the transcriptional and metabolite levels of the penicillin, sterigmatocystin, and orsellinic acid biosynthesis gene clusters were detected. These effects were due mainly to the substitution of the acetylatable lysine 14 of histone H3 and were enhanced in a lysine 14/lysine 9 double mutant of histone H3. Taken together, our findings show a causal linkage between the acetylation of lysine residue 14 of histone H3 and the transcription and product formation of secondary metabolite gene clusters.

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Wink, Michael. "Plant Secondary Metabolism: Diversity, Function and its Evolution." Natural Product Communications 3, no. 8 (August 2008): 1934578X0800300. http://dx.doi.org/10.1177/1934578x0800300801.

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A typical character of plants is the production and storage of usually complex mixtures of secondary metabolites (SM). The main function of secondary metabolites is defense against herbivores and microbes; some SM are signal compounds to attract pollinating and seed dispersing animals or play a role in the symbiotic relationships with plants and microbes. The distribution of SM in the plant kingdom shows an interesting pattern. A specific SM is often confined to a particular systematic unit, but isolated occurrences can occur in widely unrelated taxonomic groups. This review tries to explain the patchy occurrence of SM in plants. It could be due to convergent evolution, but evidence is provided that the genes that encode the biosynthesis of SM appear to have a much wider distribution than the actual secondary metabolite. It seems to be rather a matter of differential gene regulation whether a pathway is active and expressed in a given taxonomic unit or not. It is speculated that the genes of some pathways derived from an early horizontal gene transfer from bacteria, which later became mitochondria and chloroplasts. These genes/pathways should be present in most if not all land plants. About 80% of plants live in close symbiotic relationships with symbiotic fungi (ectomycorrhiza, endophytes). Recent evidence is presented that these fungi can either directly produce SM, which were formerly considered as plant SM or that these fungi have transferred the corresponding pathway gene to the host plant. The fungal contribution could also explain part of the patchy occurrence patterns of several secondary metabolites.

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FUNK, C., K. MOSBACH, and P. BRODELIUS. "Effects of a Fungal Glucan Preparation (Elicitor) on Secondary Metabolism in Plant Cell Cultures." Annals of the New York Academy of Sciences 501, no. 1 Enzyme Engine (June 1987): 347–49. http://dx.doi.org/10.1111/j.1749-6632.1987.tb45734.x.

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Motoyama, Takayuki, and Hiroyuki Osada. "Biosynthetic approaches to creating bioactive fungal metabolites: Pathway engineering and activation of secondary metabolism." Bioorganic & Medicinal Chemistry Letters 26, no. 24 (December 2016): 5843–50. http://dx.doi.org/10.1016/j.bmcl.2016.11.013.

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Tian, Fei, Sang Yoo Lee, So Young Woo, Hwa Young Choi, and Hyang Sook Chun. "A float culture method for fungal secondary metabolism study using hydrophilic polyvinylidene fluoride membranes." Analytical Biochemistry 599 (June 2020): 113722. http://dx.doi.org/10.1016/j.ab.2020.113722.

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27

Gloer, James B. "The chemistry of fungal antagonism and defense." Canadian Journal of Botany 73, S1 (December 31, 1995): 1265–74. http://dx.doi.org/10.1139/b95-387.

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Mechanisms of fungal antagonism and defense often include the production of biologically active metabolites by one species that exert effects on potential competitors and (or) predators. Studies carried out in our laboratory and others clearly indicate that such ecological phenomena can serve as valuable leads to the discovery of novel and potentially useful bioactive fungal metabolites. There is evidence that some of these compounds may render advantages to the producing organism, although careful and definitive ecological studies are required to determine this. Nevertheless, the results summarized here demonstrate the broad array of possible benefits that can arise from interdisciplinary studies in this area. This paper focuses primarily on our own investigations of the chemistry involved in fungal antagonism and defense using coprophilous and sclerotial fungi as model systems. These results have potential implications in many areas of study, including fungal ecology, secondary metabolism, chemotaxonomy, organic chemistry, structure determination, antifungal chemotherapy, and insect control. Key words: fungi, antifungal, insecticide, antagonism, chemical defense, secondary metabolites.

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Rahnama, Mostafa, Paul Maclean, Damien J. Fleetwood, and Richard D. Johnson. "VelA and LaeA are Key Regulators of Epichloë festucae Transcriptomic Response during Symbiosis with Perennial Ryegrass." Microorganisms 8, no. 1 (December 23, 2019): 33. http://dx.doi.org/10.3390/microorganisms8010033.

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VelA (or VeA) is a key global regulator in fungal secondary metabolism and development which we previously showed is required during the symbiotic interaction of Epichloë festucae with perennial ryegrass. In this study, comparative transcriptomic analyses of ∆velA mutant compared to wild-type E. festucae, under three different conditions (in culture, infected seedlings, and infected mature plants), were performed to investigate the impact of VelA on E. festucae transcriptome. These comparative transcriptomic studies showed that VelA regulates the expression of genes encoding proteins involved in membrane transport, fungal cell wall biosynthesis, host cell wall degradation, and secondary metabolism, along with a number of small secreted proteins and a large number of proteins with no predictable functions. In addition, these results were compared with previous transcriptomic experiments that studied the impact of LaeA, another key global regulator of secondary metabolism and development that we have shown is important for E. festucae–perennial ryegrass interaction. The results showed that although VelA and LaeA regulate a subset of E. festucae genes in a similar manner, they also regulated many other genes independently of each other suggesting specialised roles.

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Gluck-Thaler, Emile, Sajeet Haridas, Manfred Binder, Igor V. Grigoriev, Pedro W. Crous, Joseph W. Spatafora, Kathryn Bushley, and Jason C. Slot. "The Architecture of Metabolism Maximizes Biosynthetic Diversity in the Largest Class of Fungi." Molecular Biology and Evolution 37, no. 10 (May 18, 2020): 2838–56. http://dx.doi.org/10.1093/molbev/msaa122.

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Abstract Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales. Here, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered the most phylogenetically diverse class of fungi and known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation among sets of BGCs in individual genomes is due to nonoverlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi. We project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.

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Meister, Thieme, Thieme, Köhler, Schmitt, Valerius, and Braus. "COP9 Signalosome Interaction with UspA/Usp15 Deubiquitinase Controls VeA-Mediated Fungal Multicellular Development." Biomolecules 9, no. 6 (June 18, 2019): 238. http://dx.doi.org/10.3390/biom9060238.

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COP9 signalosome (CSN) and Den1/A deneddylases physically interact and promote multicellular development in fungi. CSN recognizes Skp1/cullin-1/Fbx E3 cullin-RING ligases (CRLs) without substrate and removes their posttranslational Nedd8 modification from the cullin scaffold. This results in CRL complex disassembly and allows Skp1 adaptor/Fbx receptor exchange for altered substrate specificity. We characterized the novel ubiquitin-specific protease UspA of the mold Aspergillus nidulans, which corresponds to CSN-associated human Usp15 and interacts with six CSN subunits. UspA reduces amounts of ubiquitinated proteins during fungal development, and the uspA gene expression is repressed by an intact CSN. UspA is localized in proximity to nuclei and recruits proteins related to nuclear transport and transcriptional processing, suggesting functions in nuclear entry control. UspA accelerates the formation of asexual conidiospores, sexual development, and supports the repression of secondary metabolite clusters as the derivative of benzaldehyde (dba) genes. UspA reduces protein levels of the fungal NF-kappa B-like velvet domain protein VeA, which coordinates differentiation and secondary metabolism. VeA stability depends on the Fbx23 receptor, which is required for light controlled development. Our data suggest that the interplay between CSN deneddylase, UspA deubiquitinase, and SCF-Fbx23 ensures accurate levels of VeA to support fungal development and an appropriate secondary metabolism.

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Nielsen, Jens Christian, and Jens Nielsen. "Development of fungal cell factories for the production of secondary metabolites: Linking genomics and metabolism." Synthetic and Systems Biotechnology 2, no. 1 (March 2017): 5–12. http://dx.doi.org/10.1016/j.synbio.2017.02.002.

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Gerke, Jennifer, Özgür Bayram, and Gerhard H. Braus. "Fungal S-adenosylmethionine synthetase and the control of development and secondary metabolism in Aspergillus nidulans." Fungal Genetics and Biology 49, no. 6 (June 2012): 443–54. http://dx.doi.org/10.1016/j.fgb.2012.04.003.

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Imazaki, Ai, Aiko Tanaka, Yoshiaki Harimoto, Mikihiro Yamamoto, Kazuya Akimitsu, Pyoyun Park, and Takashi Tsuge. "Contribution of Peroxisomes to Secondary Metabolism and Pathogenicity in the Fungal Plant Pathogen Alternaria alternata." Eukaryotic Cell 9, no. 5 (March 26, 2010): 682–94. http://dx.doi.org/10.1128/ec.00369-09.

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ABSTRACT The filamentous fungus Alternaria alternata includes seven pathogenic variants (pathotypes) which produce different host-selective toxins and cause diseases on different plants. The Japanese pear pathotype produces the host-selective AK-toxin, an epoxy-decatrienoic acid ester, and causes black spot of Japanese pear. Previously, we identified four genes, AKT1, AKT2, AKT3, and AKTR, involved in AK toxin biosynthesis. AKT1, AKT2, and AKT3 encode enzyme proteins with peroxisomal targeting signal type 1 (PTS1)-like tripeptides, SKI, SKL, and PKL, respectively, at the C-terminal ends. In this study, we verified the peroxisome localization of Akt1, Akt2, and Akt3 by using strains expressing N-terminal green fluorescent protein (GFP)-tagged versions of the proteins. To assess the role of peroxisome function in AK-toxin production, we isolated AaPEX6, which encodes a peroxin protein essential for peroxisome biogenesis, from the Japanese pear pathotype and made AaPEX6 disruption-containing transformants from a GFP-Akt1-expressing strain. The ΔAaPEX6 mutant strains did not grow on fatty acid media because of a defect in fatty acid β oxidation. The import of GFP-Akt1 into peroxisomes was impaired in the ΔAaPEX6 mutant strains. These strains completely lost AK toxin production and pathogenicity on susceptible pear leaves. These data show that peroxisomes are essential for AK-toxin biosynthesis. The ΔAaPEX6 mutant strains showed a marked reduction in the ability to cause lesions on leaves of a resistant pear cultivar with defense responses compromised by heat shock. This result suggests that peroxisome function is also required for plant invasion and tissue colonization in A. alternata. We also observed that mutation of AaPEX6 caused a marked reduction of conidiation.

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Khan, Naseem I., Brent Tisserat, Mark Berhow, and Steven F. Vaughn. "Influence of Autoclaved Fungal Materials on Spearmint (Mentha spicata L.) Growth, Morphogenesis, and Secondary Metabolism." Journal of Chemical Ecology 31, no. 7 (July 2005): 1579–93. http://dx.doi.org/10.1007/s10886-005-5799-7.

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Motoyama, Takayuki. "Secondary Metabolites of the Rice Blast Fungus Pyricularia oryzae: Biosynthesis and Biological Function." International Journal of Molecular Sciences 21, no. 22 (November 18, 2020): 8698. http://dx.doi.org/10.3390/ijms21228698.

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Plant pathogenic fungi produce a wide variety of secondary metabolites with unique and complex structures. However, most fungal secondary metabolism genes are poorly expressed under laboratory conditions. Moreover, the relationship between pathogenicity and secondary metabolites remains unclear. To activate silent gene clusters in fungi, successful approaches such as epigenetic control, promoter exchange, and heterologous expression have been reported. Pyricularia oryzae, a well-characterized plant pathogenic fungus, is the causal pathogen of rice blast disease. P. oryzae is also rich in secondary metabolism genes. However, biosynthetic genes for only four groups of secondary metabolites have been well characterized in this fungus. Biosynthetic genes for two of the four groups of secondary metabolites have been identified by activating secondary metabolism. This review focuses on the biosynthesis and roles of the four groups of secondary metabolites produced by P. oryzae. These secondary metabolites include melanin, a polyketide compound required for rice infection; pyriculols, phytotoxic polyketide compounds; nectriapyrones, antibacterial polyketide compounds produced mainly by symbiotic fungi including endophytes and plant pathogens; and tenuazonic acid, a well-known mycotoxin produced by various plant pathogenic fungi and biosynthesized by a unique NRPS-PKS enzyme.

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Nowak, Monika, Przemysław Bernat, Julia Mrozińska, and Sylwia Różalska. "Acetamiprid Affects Destruxins Production but Its Accumulation in Metarhizium sp. Spores Increases Infection Ability of Fungi." Toxins 12, no. 9 (September 11, 2020): 587. http://dx.doi.org/10.3390/toxins12090587.

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Metarhizium sp. are entomopathogenic fungi that inhabit the soil environment. Together, they act as natural pest control factors. In the natural environment, they come into contact with various anthropogenic pollutants, and sometimes, they are used together and interchangeably with chemical insecticides (e.g., neonicotinoids) for pest control. In most cases, the compatibility of entomopathogens with insecticides has been determined; however, the influence of these compounds on the metabolism of entomopathogenic fungi has not yet been studied. Secondary metabolites are very important factors that influence the fitness of the producers, playing important roles in the ability of these pathogens to successfully parasitize insects. In this study, for the first time, we focus on whether the insecticide present in the fungal growth environment affects secondary metabolism in fungi. The research revealed that acetamiprid at concentrations from 5 to 50 mg L−1 did not inhibit the growth of all tested Metarhizium sp.; however, it reduced the level of 19 produced destruxins in direct proportion to the dosage used. Furthermore, it was shown that acetamiprid accumulates not only in plant or animal tissues, but also in fungal cells. Despite the negative impact of acetamiprid on secondary metabolism, it was proofed to accumulate in Metarhizium spores, which appeared to have a stronger infectious potential against mealworm Tenebrio molitor, in comparison to the insecticide or the biological agent alone.

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Marzluf, G. A. "Genetic regulation of nitrogen metabolism in the fungi." Microbiology and Molecular Biology Reviews 61, no. 1 (March 1997): 17–32. http://dx.doi.org/10.1128/mmbr.61.1.17-32.1997.

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In the fungi, nitrogen metabolism is controlled by a complex genetic regulatory circuit which ensures the preferential use of primary nitrogen sources and also confers the ability to use many different secondary nitrogen sources when appropriate. Most structural genes encoding nitrogen catabolic enzymes are subject to nitrogen catabolite repression, mediated by positive-acting transcription factors of the GATA family of proteins. However, certain GATA family members, such as the yeast DAL80 factor, act negatively to repress gene expression. Selective expression of the genes which encode enzymes for the metabolism of secondary nitrogen sources is often achieved by induction, mediated by pathway-specific factors, many of which have a GAL4-like C6/Zn2 DNA binding domain. Regulation within the nitrogen circuit also involves specific protein-protein interactions, as exemplified by the specific binding of the negative-acting NMR protein with the positive-acting NIT2 protein of Neurospora crassa. Nitrogen metabolic regulation appears to play a significant role in the pathogenicity of certain animal and plant fungal pathogens.

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Cary, J. W., Z. Han, Y. Yin, J. M. Lohmar, S. Shantappa, P. Y. Harris-Coward, B. Mack, et al. "Transcriptome Analysis of Aspergillus flavus RevealsveA-Dependent Regulation of Secondary Metabolite Gene Clusters, Including the Novel Aflavarin Cluster." Eukaryotic Cell 14, no. 10 (July 24, 2015): 983–97. http://dx.doi.org/10.1128/ec.00092-15.

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ABSTRACTThe global regulatoryveAgene governs development and secondary metabolism in numerous fungal species, includingAspergillus flavus. This is especially relevant sinceA. flavusinfects crops of agricultural importance worldwide, contaminating them with potent mycotoxins. The most well-known are aflatoxins, which are cytotoxic and carcinogenic polyketide compounds. The production of aflatoxins and the expression of genes implicated in the production of these mycotoxins areveAdependent. The genes responsible for the synthesis of aflatoxins are clustered, a signature common for genes involved in fungal secondary metabolism. Studies of theA. flavusgenome revealed many gene clusters possibly connected to the synthesis of secondary metabolites. Many of these metabolites are still unknown, or the association between a known metabolite and a particular gene cluster has not yet been established. In the present transcriptome study, we show thatveAis necessary for the expression of a large number of genes. Twenty-eight out of the predicted 56 secondary metabolite gene clusters include at least one gene that is differentially expressed depending on presence or absence ofveA. One of the clusters under the influence ofveAis cluster 39. The absence ofveAresults in a downregulation of the five genes found within this cluster. Interestingly, our results indicate that the cluster is expressed mainly in sclerotia. Chemical analysis of sclerotial extracts revealed that cluster 39 is responsible for the production of aflavarin.

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ASAI, Teigo, and Yoshiteru OSHIMA. "Epigenetic Regulation of Fungal Secondary Metabolism, and Production of Structurally Diverse Natural Products Using Epigenetic Modifiers." KAGAKU TO SEIBUTSU 51, no. 1 (2013): 13–21. http://dx.doi.org/10.1271/kagakutoseibutsu.51.13.

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Higgins, Steven A., Christopher W. Schadt, Patrick B. Matheny, and Frank E. Löffler. "Phylogenomics Reveal the Dynamic Evolution of Fungal Nitric Oxide Reductases and Their Relationship to Secondary Metabolism." Genome Biology and Evolution 10, no. 9 (August 29, 2018): 2474–89. http://dx.doi.org/10.1093/gbe/evy187.

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Xu, Xiaodi, Yong Chen, Boqiang Li, and Shiping Tian. "Arginine Methyltransferase PeRmtC Regulates Development and Pathogenicity of Penicillium expansum via Mediating Key Genes in Conidiation and Secondary Metabolism." Journal of Fungi 7, no. 10 (September 27, 2021): 807. http://dx.doi.org/10.3390/jof7100807.

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Penicillium expansum is one of the most common and destructive post-harvest fungal pathogens that can cause blue mold rot and produce mycotoxins in fruit, leading to significant post-harvest loss and food safety concerns. Arginine methylation by protein arginine methyltransferases (PRMTs) modulates various cellular processes in many eukaryotes. However, the functions of PRMTs are largely unknown in post-harvest fungal pathogens. To explore their roles in P. expansum, we identified four PRMTs (PeRmtA, PeRmtB, PeRmtC, and PeRmt2). The single deletion of PeRmtA, PeRmtB, or PeRmt2 had minor or no impact on the P. expansum phenotype while deletion of PeRmtC resulted in decreased conidiation, delayed conidial germination, impaired pathogenicity and pigment biosynthesis, and altered tolerance to environmental stresses. Further research showed that PeRmtC could regulate two core regulatory genes, PeBrlA and PeAbaA, in conidiation, a series of backbone genes in secondary metabolism, and affect the symmetric ω-NG, N’G-dimethylarginine (sDMA) modification of proteins with molecular weights of primarily 16–17 kDa. Collectively, this work functionally characterized four PRMTs in P. expansum and showed the important roles of PeRmtC in the development, pathogenicity, and secondary metabolism of P. expansum.

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Hashemabadi, Davood, Fatemeh Sabzevari, Behzad Kaviani, and Mohammad Hossein Ansari. "Organic N-fertilizer, rhizobacterial inoculation and fungal compost improve nutrient uptake, plant growth and the levels of vindoline, ajmalicine, vinblastine, catharanthine and total alkaloids in Catharanthus roseus L." Folia Horticulturae 30, no. 2 (December 1, 2018): 203–13. http://dx.doi.org/10.2478/fhort-2018-0018.

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Abstract The aim of the study was to replace mineral fertilizers with organic and biological fertilizers to improve nutrient uptake, plant growth and the concentrations of some important secondary metabolites in periwinkle (Catharanthus roseus L.). Periwinkle plants were grown under different rates of N supply (0, 20 and 40 mg kg−1 soil) and biological treatments (Azospirillum, Azotobacter, Azospirillum plus Azotobacter, Azospirillum plus fungal compost, Azotobacter plus fungal compost, and fungal compost). The concentrations of pigments and nutrients were measured by spectrophotometry and flame photometry. Secondary metabolites were analyzed by high-performance liquid chromatography (HPLC). Data were recorded for plant growth and development parameters, nutrient uptake and some secondary metabolites of periwinkle plants. The results showed that the N-fertilizer and biological treatments significantly improved most growth attributes and nutrient uptake and increased the concentrations of secondary metabolites as compared to the control. Maximum concentrations of root ajmalicine (0.54 mg g−1 DW), leaf vinblastine (0.96 mg g−1 DW) and root catharanthine (2.38 mg g−1 DW) were obtained from the treatment with Azospirillum under N-fertilizer at 20 and 40 mg kg−1 soil. Azotobacter along with fungal compost under N-fertilizer at 40 mg kg−1 soil induced the maximum concentration of leaf vindoline (1.94 mg g−1 DW). The highest concentration of root alkaloids (1.11 mg g−1 DW) was obtained from the treatment with compost under 40 mg N kg−1 soil. Azospirillum, Azotobacter and fungal compost combined with the N-fertilizer improved many morphological and nutrient characteristics. In conclusion, the growth and metabolism of C. roseus were significantly positively affected by the organic and biological fertilizers.

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Alvi, Madiha M., David S. Meyer, Nicholas J. Hardin, James G. deKay, Annis M. Marney, and Matthew P. Gilbert. "AspergillusThyroiditis: A Complication of Respiratory Tract Infection in an Immunocompromised Patient." Case Reports in Endocrinology 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/741041.

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A 59-year-old male with past medical history significant for non-Hodgkin’s lymphoma status after chemotherapy presented with acute onset of neck pain, odynophagia, and dysphagia associated with subjective fever, chills, and dyspnea. Physical findings included a temperature of 38.4°C, hypertension, and tachycardia. Patient was found to have anterior neck tenderness. Laboratory evaluation revealed neutropenia. The patient was started on empiric antibacterial and antiviral therapy and continued on home prophylactic antifungal treatment. Thyroid function tests revealed overt hyperthyroidism. A thyroid ultrasound showed heterogeneous echotexture without discrete nodules. Subacute thyroiditis was treated with methylprednisolone, metoprolol, and opiate analgesics. Patient’s antibacterial, antifungal, and antiviral treatments were broadened. A fine needle aspiration was not conducted. The patient’s condition deteriorated rapidly over his brief hospital course and he expired. Autopsy showed fungal thyroiditis secondary to disseminated invasiveAspergillus. This report describes the presentation of fungal thyroiditis secondary to disseminated invasiveAspergillusoriginating from the respiratory tract. The authors review the diagnostic challenges, pathophysiology, and treatment of this condition.

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Wang, Xiuna, Wenjie Zha, Linlin Liang, Opemipo Esther Fasoyin, Lihan Wu, and Shihua Wang. "The bZIP Transcription Factor AflRsmA Regulates Aflatoxin B1 Biosynthesis, Oxidative Stress Response and Sclerotium Formation in Aspergillus flavus." Toxins 12, no. 4 (April 23, 2020): 271. http://dx.doi.org/10.3390/toxins12040271.

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Fungal secondary metabolites play important roles not only in fungal ecology but also in humans living as beneficial medicine or harmful toxins. In filamentous fungi, bZIP-type transcription factors (TFs) are associated with the proteins involved in oxidative stress response and secondary metabolism. In this study, a connection between a bZIP TF and oxidative stress induction of secondary metabolism is uncovered in an opportunistic pathogen Aspergillus flavus, which produces carcinogenic and mutagenic aflatoxins. The bZIP transcription factor AflRsmA was identified by a homology research of A. flavus genome with the bZIP protein RsmA, involved in secondary metabolites production in Aspergillus nidulans. The AflrsmA deletion strain (ΔAflrsmA) displayed less sensitivity to the oxidative reagents tert-Butyl hydroperoxide (tBOOH) in comparison with wild type (WT) and AflrsmA overexpression strain (AflrsmAOE), while AflrsmAOE strain increased sensitivity to the oxidative reagents menadione sodium bisulfite (MSB) compared to WT and ΔAflrsmA strains. Without oxidative treatment, aflatoxin B1 (AFB1) production of ΔAflrsmA strains was consistent with that of WT, but AflrsmAOE strain produced more AFB1 than WT; tBOOH and MSB treatment decreased AFB1 production of ΔAflrsmA compared to WT. Besides, relative to WT, ΔAflrsmA strain decreased sclerotia, while AflrsmAOE strain increased sclerotia. The decrease of AFB1 by ΔAflrsmA but increase of AFB1 by AflrsmAOE was on corn. Our results suggest that AFB1 biosynthesis is regulated by AflRsmA by oxidative stress pathways and provide insights into a possible function of AflRsmA in mediating AFB1 biosynthesis response host defense in pathogen A. flavus.

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Lind, Abigail L., Jennifer H. Wisecaver, Timothy D. Smith, Xuehuan Feng, Ana M. Calvo, and Antonis Rokas. "Examining the Evolution of the Regulatory Circuit Controlling Secondary Metabolism and Development in the Fungal Genus Aspergillus." PLOS Genetics 11, no. 3 (March 18, 2015): e1005096. http://dx.doi.org/10.1371/journal.pgen.1005096.

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Zhang, Han, Antonis Rokas, and Jason C. Slot. "Two Different Secondary Metabolism Gene Clusters Occupied the Same Ancestral Locus in Fungal Dermatophytes of the Arthrodermataceae." PLoS ONE 7, no. 7 (July 30, 2012): e41903. http://dx.doi.org/10.1371/journal.pone.0041903.

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Ito, Kaoru, Takayoshi Tanaka, Rieko Hatta, Mikihiro Yamamoto, Kazuya Akimitsu, and Takashi Tsuge. "Dissection of the host range of the fungal plant pathogen Alternaria alternata by modification of secondary metabolism." Molecular Microbiology 52, no. 2 (March 19, 2004): 399–411. http://dx.doi.org/10.1111/j.1365-2958.2004.04004.x.

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Barahona, Emma, Ana Navazo, Francisco Martínez-Granero, Teresa Zea-Bonilla, Rosa María Pérez-Jiménez, Marta Martín, and Rafael Rivilla. "Pseudomonas fluorescens F113 Mutant with Enhanced Competitive Colonization Ability and Improved Biocontrol Activity against Fungal Root Pathogens." Applied and Environmental Microbiology 77, no. 15 (June 17, 2011): 5412–19. http://dx.doi.org/10.1128/aem.00320-11.

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ABSTRACTMotility is one of the most important traits for efficient rhizosphere colonization byPseudomonas fluorescensF113rif (F113). In this bacterium, motility is a polygenic trait that is repressed by at least three independent pathways, including the Gac posttranscriptional system, the Wsp chemotaxis-like pathway, and the SadB pathway. Here we show that thekinBgene, which encodes a signal transduction protein that together with AlgB has been implicated in alginate production, participates in swimming motility repression through the Gac pathway, acting downstream of the GacAS two-component system. Gac mutants are impaired in secondary metabolite production and are unsuitable as biocontrol agents. However, thekinBmutant and a triple mutant affected inkinB,sadB, andwspR(KSW) possess a wild-type phenotype for secondary metabolism. The KSW strain is hypermotile and more competitive for rhizosphere colonization than the wild-type strain. We have compared the biocontrol activity of KSW with those of the wild-type strain and a phenotypic variant (F113v35 [V35]) which is hypermotile and hypercompetitive but is affected in secondary metabolism since it harbors agacSmutation. Biocontrol experiments in theFusarium oxysporumf. sp.radicis-lycopersici/Lycopersicum esculentum(tomato) andPhytophthora cactorum/Fragaria vesca(strawberry) pathosystems have shown that the three strains possess biocontrol activity. Biocontrol activity was consistently lower for V35, indicating that the production of secondary metabolites was the most important trait for biocontrol. Strain KSW showed improved biocontrol compared with the wild-type strain, indicating that an increase in competitive colonization ability resulted in improved biocontrol and that the rational design of biocontrol agents by mutation is feasible.

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Gerke, Jennifer, Özgür Bayram, and Gerhard H. Braus. "Corrigendum to ‘Fungal S-adenosylmethionine synthetase and the control of development and secondary metabolism in Aspergillus nidulans’. [Fungal Genet. Biol. 49 (2012) 443–454]." Fungal Genetics and Biology 136 (March 2020): 103331. http://dx.doi.org/10.1016/j.fgb.2019.103331.

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Steenwyk, Jacob L., Matthew E. Mead, Sonja L. Knowles, Huzefa A. Raja, Christopher D. Roberts, Oliver Bader, Jos Houbraken, Gustavo H. Goldman, Nicholas H. Oberlies, and Antonis Rokas. "Variation Among Biosynthetic Gene Clusters, Secondary Metabolite Profiles, and Cards of Virulence Across Aspergillus Species." Genetics 216, no. 2 (August 17, 2020): 481–97. http://dx.doi.org/10.1534/genetics.120.303549.

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Aspergillus fumigatus is a major human pathogen. In contrast, Aspergillus fischeri and the recently described Aspergillus oerlinghausenensis, the two species most closely related to A. fumigatus, are not known to be pathogenic. Some of the genetic determinants of virulence (or “cards of virulence”) that A. fumigatus possesses are secondary metabolites that impair the host immune system, protect from host immune cell attacks, or acquire key nutrients. To examine whether secondary metabolism-associated cards of virulence vary between these species, we conducted extensive genomic and secondary metabolite profiling analyses of multiple A. fumigatus, one A. oerlinghausenensis, and multiple A. fischeri strains. We identified two cards of virulence (gliotoxin and fumitremorgin) shared by all three species and three cards of virulence (trypacidin, pseurotin, and fumagillin) that are variable. For example, we found that all species and strains examined biosynthesized gliotoxin, which is known to contribute to virulence, consistent with the conservation of the gliotoxin biosynthetic gene cluster (BGC) across genomes. For other secondary metabolites, such as fumitremorgin, a modulator of host biology, we found that all species produced the metabolite but that there was strain heterogeneity in its production within species. Finally, species differed in their biosynthesis of fumagillin and pseurotin, both contributors to host tissue damage during invasive aspergillosis. A. fumigatus biosynthesized fumagillin and pseurotin, while A. oerlinghausenensis biosynthesized fumagillin and A. fischeri biosynthesized neither. These biochemical differences were reflected in sequence divergence of the intertwined fumagillin/pseurotin BGCs across genomes. These results delineate the similarities and differences in secondary metabolism-associated cards of virulence between a major fungal pathogen and its nonpathogenic closest relatives, shedding light onto the genetic and phenotypic changes associated with the evolution of fungal pathogenicity.

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Journal articles on the topic 'Fungal secondary metabolism'

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