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FEMS Microbiology Reviews Jan 2012Major insights into sexual development and cryptic sexuality within filamentous fungi have been gained from investigations using Aspergillus species. Here, an overview... (Review)
Review
Major insights into sexual development and cryptic sexuality within filamentous fungi have been gained from investigations using Aspergillus species. Here, an overview is first given into sexual morphogenesis in the aspergilli, describing the different types of sexual structures formed and how their production is influenced by a variety of environmental and nutritional factors. It is argued that the formation of cleistothecia and accessory tissues, such as Hülle cells and sclerotia, should be viewed as two independent but co-ordinated developmental pathways. Next, a comprehensive survey of over 75 genes associated with sexual reproduction in the aspergilli is presented, including genes relating to mating and the development of cleistothecia, sclerotia and ascospores. Most of these genes have been identified from studies involving the homothallic Aspergillus nidulans, but an increasing number of studies have now in addition characterized 'sex-related' genes from the heterothallic species Aspergillus fumigatus and Aspergillus flavus. A schematic developmental genetic network is proposed showing the inter-relatedness between these genes. Finally, the discovery of sexual reproduction in certain Aspergillus species that were formerly considered to be strictly asexual is reviewed, and the importance of these findings for cryptic sexuality in the aspergilli as a whole is discussed.
Topics: Aspergillus; Cell Division; Gene Expression Regulation, Fungal; Genes, Mating Type, Fungal; Recombination, Genetic
PubMed: 22091779
DOI: 10.1111/j.1574-6976.2011.00308.x -
Current Biology : CB Jul 2020Interspecific hybridization substantially alters genotypes and phenotypes and can give rise to new lineages. Hybrid isolates that differ from their parental species in...
Interspecific hybridization substantially alters genotypes and phenotypes and can give rise to new lineages. Hybrid isolates that differ from their parental species in infection-relevant traits have been observed in several human-pathogenic yeasts and plant-pathogenic filamentous fungi but have yet to be found in human-pathogenic filamentous fungi. We discovered 6 clinical isolates from patients with aspergillosis originally identified as Aspergillus nidulans (section Nidulantes) that are actually allodiploid hybrids formed by the fusion of Aspergillus spinulosporus with an unknown close relative of Aspergillus quadrilineatus, both in section Nidulantes. Evolutionary genomic analyses revealed that these isolates belong to Aspergillus latus, an allodiploid hybrid species. Characterization of diverse infection-relevant traits further showed that A. latus hybrid isolates are genomically and phenotypically heterogeneous but also differ from A. nidulans, A. spinulosporus, and A. quadrilineatus. These results suggest that allodiploid hybridization contributes to the genomic and phenotypic diversity of filamentous fungal pathogens of humans.
Topics: Aspergillus; Diploidy; Genome, Fungal; Genomics; Hybridization, Genetic
PubMed: 32502407
DOI: 10.1016/j.cub.2020.04.071 -
Applied Microbiology and Biotechnology Apr 2019Citric acid production by Aspergillus niger and itaconic acid production by Aspergillus terreus are two major examples of technical scale fungal fermentations based on... (Review)
Review
Citric acid production by Aspergillus niger and itaconic acid production by Aspergillus terreus are two major examples of technical scale fungal fermentations based on metabolic overflow of primary metabolism. Both organic acids are formed by the same metabolic pathway, but whereas citric acid is the end product in A. niger, A. terreus performs two additional enzymatic steps leading to itaconic acid. Despite of this high similarity, the optimization of the production process and the mechanism and regulation of overflow of these two acids has mostly been investigated independently, thereby ignoring respective knowledge from the other. In this review, we will highlight where the similarities and the real differences of these two processes occur, which involves various aspects of medium composition, metabolic regulation and compartmentation, transcriptional regulation, and gene evolution. These comparative data may facilitate further investigations of citric acid and itaconic acid accumulation and may contribute to improvements in their industrial production.
Topics: Aspergillus; Aspergillus niger; Citric Acid; Fermentation; Metabolic Networks and Pathways; Succinates
PubMed: 30758523
DOI: 10.1007/s00253-018-09607-9 -
Applied and Environmental Microbiology Nov 2021Ergot alkaloids derived from lysergic acid have impacted humanity as contaminants of crops and as the bases of pharmaceuticals prescribed to treat dementia, migraines,...
Ergot alkaloids derived from lysergic acid have impacted humanity as contaminants of crops and as the bases of pharmaceuticals prescribed to treat dementia, migraines, and other disorders. Several plant-associated fungi in the Clavicipitaceae produce lysergic acid derivatives, but many of these fungi are difficult to culture and manipulate. Some Aspergillus species, which may be more ideal experimental and industrial organisms, contain an alternate branch of the ergot alkaloid pathway, but none were known to produce lysergic acid derivatives. We mined the genomes of Aspergillus species for ergot alkaloid synthesis () gene clusters and discovered that three species, A. leporis, A. homomorphus, and A. hancockii, had clusters indicative of the capacity to produce a lysergic acid amide. In culture, , , and produced lysergic acid amides, predominantly lysergic acid α-hydroxyethylamide (LAH). Aspergillus leporis and produced high concentrations of LAH and secreted most of their ergot alkaloid yield into the culture medium. Phylogenetic analyses indicated that genes encoding enzymes leading to the synthesis of lysergic acid were orthologous to those of the lysergic acid amide-producing Clavicipitaceae; however, genes to incorporate lysergic acid into an amide derivative evolved from different ancestral genes in the Aspergillus species. Our data demonstrate that fungi outside the Clavicipitaceae produce lysergic acid amides and indicate that the capacity to produce lysergic acid evolved once, but the ability to insert it into LAH evolved independently in Aspergillus species and the Clavicipitaceae. The LAH-producing Aspergillus species may be useful for the study and production of these pharmaceutically important compounds. Lysergic acid derivatives are specialized metabolites with historical, agricultural, and medical significance and were known heretofore only from fungi in one family, the Clavicipitaceae. Our data show that several Aspergillus species, representing a different family of fungi, also produce lysergic acid derivatives and that the ability to put lysergic acid into its amide forms evolved independently in the two lineages of fungi. From microbiological and pharmaceutical perspectives, the Aspergillus species may represent better experimental and industrial organisms than the currently employed lysergic acid producers of the plant-associated Clavicipitaceae. The observation that both lineages independently evolved the derivative lysergic acid α-hydroxyethylamide (LAH), among many possible lysergic acid amides, suggests selection for this metabolite.
Topics: Amides; Aspergillus; Biological Evolution; Hypocreales; Lysergic Acid; Lysergic Acid Diethylamide; Phylogeny
PubMed: 34586904
DOI: 10.1128/AEM.01801-21 -
Biotechnology Letters Mar 2011Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during... (Review)
Review
Aspergilli have a long history in biotechnology as expression platforms for the production of food ingredients, pharmaceuticals and enzymes. The achievements made during the last years, however, have the potential to revolutionize Aspergillus biotechnology and to assure Aspergillus a dominant place among microbial cell factories. This mini-review will highlight most recent breakthroughs in fundamental and applied Aspergillus research with a focus on new molecular tools, techniques and products. New trends and concepts related to Aspergillus genomics and systems biology will be discussed as well as the challenges that have to be met to integrate omics data with metabolic engineering attempts.
Topics: Aspergillus; Biotechnology; Genetic Engineering; Genomics; Systems Biology
PubMed: 21088867
DOI: 10.1007/s10529-010-0473-8 -
Microbiology Spectrum Feb 2023For Aspergillus flavus, a pathogen of considerable economic and health concern, successful gene knockout work for more than a decade has relied nearly exclusively on...
A Simple CRISPR/Cas9 System for Efficiently Targeting Genes of Aspergillus Section Species, Aspergillus nidulans, Aspergillus fumigatus, Aspergillus terreus, and Aspergillus niger.
For Aspergillus flavus, a pathogen of considerable economic and health concern, successful gene knockout work for more than a decade has relied nearly exclusively on using nonhomologous end-joining pathway (NHEJ)-deficient recipients via forced double-crossover recombination of homologous sequences. In this study, a simple CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease) genome editing system that gave extremely high (>95%) gene-targeting frequencies in A. flavus was developed. It contained a shortened Aspergillus nidulans autonomously replicating sequence that maintained good transformation frequencies and Aspergillus oryzae as the selection marker for pyrithiamine resistance. Expression of the codon-optimized gene was driven by the A. nidulans promoter and terminator. Expression of single guide RNA (sgRNA) cassettes was controlled by the A. flavus U6 promoter and terminator. The high transformation and gene-targeting frequencies of this system made generation of A. flavus gene knockouts with or without phenotypic changes effortless. Additionally, multiple-gene knockouts of A. flavus conidial pigment genes (// or //) were quickly generated by a sequential approach. Cotransforming sgRNA vectors targeting A. flavus , , and gave 52%, 40%, and 8% of single-, double-, and triple-gene knockouts, respectively. The system was readily applicable to other section aspergilli (A. parasiticus, A. oryzae, A. sojae, A. nomius, A. bombycis, and A. pseudotamarii) with comparable transformation and gene-targeting efficiencies. Moreover, it gave satisfactory gene-targeting efficiencies (>90%) in A. nidulans (section ), A. fumigatus (section ), A. terreus (section ), and A. niger (section ). It likely will have a broad application in aspergilli. CRISPR/Cas9 genome editing systems have been developed for many aspergilli. Reported gene-targeting efficiencies vary greatly and are dependent on delivery methods, repair mechanisms of induced double-stranded breaks, selection markers, and genetic backgrounds of transformation recipient strains. They are also mostly strain specific or species specific. This developed system is highly efficient and allows knocking out multiple genes in A. flavus efficiently either by sequential transformation or by cotransformation of individual sgRNA vectors if desired. It is readily applicable to section species and aspergilli in other sections ("section" is a taxonomic rank between genus and species). This cross-Aspergillus section system is for wild-type isolates and does not require homologous donor DNAs to be added, NHEJ-deficient strains to be created, or forced recycling of knockout recipients to be performed for multiple-gene targeting. Hence, it simplifies and expedites the gene-targeting process significantly.
Topics: Aspergillus fumigatus; Aspergillus niger; CRISPR-Cas Systems; Aspergillus nidulans
PubMed: 36651760
DOI: 10.1128/spectrum.04648-22 -
Scientific Reports Jan 2024Groundnuts are mostly contaminated with the mold Aspergillus flavus which produces a carcinogenic mycotoxin called as aflatoxin. It is very important to understand the...
Groundnuts are mostly contaminated with the mold Aspergillus flavus which produces a carcinogenic mycotoxin called as aflatoxin. It is very important to understand the genetic factors underlying its pathogenicity, regulation, and biosynthesis of secondary metabolites and animal toxicities, but it still lacks useful information due to certain gaps in the era of modern technology. Therefore, the present study was considered to determine the key genes and metabolites involved in the biosynthesis of aflatoxin by using a molecular approach in a virulent strain of Aspergillus. The whole genome sequence of highly toxic and virulent Aspergillus isolates JAM-JKB-B HA-GG20 revealed 3,73,54,834 bp genome size, 2, 26, 257 number of contigs with N50 value of 49,272 bp, 12,400 genes and 48.1% of GC contained respectively. The genome sequence was compared with other known aflatoxin producing and non-producing genome of Aspergillus spp. and 61 secondary metabolite (SM) gene clusters were annotated with the toxic strain JAM-JKB-BHA-GG20 which showed similarity with other Aspergillus spp. A total number of eight genes (ver-1, AflR, pksA, uvm8, omt1, nor-1, Vha and aflP) were identified related to biosynthesis of aflatoxin and ochratoxin. Also, 69 SSR with forward and reverse primers and 137 di and tri nucleotide motifs were identified in the nucleotide sequence region related to aflatoxin gene pathway. The genes and putative metabolites identified in this study are potentially involved in host invasion and pathogenicity. As such, the genomic information obtained in this study is helpful in understanding aflatoxin gene producing pathway in comparison to other Aspergillus spp. and predicted presence of other secondary metabolites clusters viz. Nrps, T1pks etc. genes associated with a biosynthesis of OTA mycotoxin.
Topics: Aspergillus flavus; Aspergillus; Aflatoxins; Genes, Fungal; Whole Genome Sequencing
PubMed: 38168670
DOI: 10.1038/s41598-023-50986-5 -
MBio Jul 2019The filamentous fungal family contains >1,000 known species, mostly in the genera and Several species are used in the food, biotechnology, and drug industries (e.g.,...
The filamentous fungal family contains >1,000 known species, mostly in the genera and Several species are used in the food, biotechnology, and drug industries (e.g., and ), while others are dangerous human and plant pathogens (e.g., and ). To infer a robust phylogeny and pinpoint poorly resolved branches and their likely underlying contributors, we used 81 genomes spanning the diversity of and to construct a 1,668-gene data matrix. Phylogenies of the nucleotide and amino acid versions of this full data matrix as well as of several additional data matrices were generated using three different maximum likelihood schemes (i.e., gene-partitioned, unpartitioned, and coalescence) and using both site-homogenous and site-heterogeneous models (total of 64 species-level phylogenies). Examination of the topological agreement among these phylogenies and measures of internode certainty identified 11/78 (14.1%) bipartitions that were incongruent and pinpointed the likely underlying contributing factors, which included incomplete lineage sorting, hidden paralogy, hybridization or introgression, and reconstruction artifacts associated with poor taxon sampling. Relaxed molecular clock analyses suggest that likely originated in the lower Cretaceous and that the and genera originated in the upper Cretaceous. Our results shed light on the ongoing debate on systematics and taxonomy and provide a robust evolutionary and temporal framework for comparative genomic analyses in More broadly, our approach provides a general template for phylogenomic identification of resolved and contentious branches in densely genome-sequenced lineages across the tree of life. Understanding the evolution of traits across technologically and medically significant fungi requires a robust phylogeny. Even though species in the and genera (family , class Eurotiomycetes) are some of the most significant technologically and medically relevant fungi, we still lack a genome-scale phylogeny of the lineage or knowledge of the parts of the phylogeny that exhibit conflict among analyses. Here, we used a phylogenomic approach to infer evolutionary relationships among 81 genomes that span the diversity of and species, to identify conflicts in the phylogeny, and to determine the likely underlying factors of the observed conflicts. Using a data matrix comprised of 1,668 genes, we found that while most branches of the phylogeny of the are robustly supported and recovered irrespective of method of analysis, a few exhibit various degrees of conflict among our analyses. Further examination of the observed conflict revealed that it largely stems from incomplete lineage sorting and hybridization or introgression. Our analyses provide a robust and comprehensive evolutionary genomic roadmap for this important lineage, which will facilitate the examination of the diverse technologically and medically relevant traits of these fungi in an evolutionary context.
Topics: Aspergillus; Biotechnology; Evolution, Molecular; Genome, Fungal; Genomics; Penicillium; Phylogeny; Sequence Analysis, DNA
PubMed: 31289177
DOI: 10.1128/mBio.00925-19 -
Medical Mycology Journal 2016Aspergillosis is an important deep mycosis. The causative agents are Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, of which A.... (Review)
Review
Aspergillosis is an important deep mycosis. The causative agents are Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, and Aspergillus terreus, of which A. fumigatus is the most prevalent. Cryptic Aspergillus spp., which morphologically resemble representative species of each Aspergillus section, also cause aspergillosis. Most of the cryptic species reveal different susceptibility patterns and/or different secondary metabolite profiles, also called exometabolome in this manuscript, from those representative species. On the other hand, azole-resistant A. fumigatus strains in clinical specimens and in the environment have been reported. Therefore, it is imperative to precisely identify the species, including cryptic Aspergillus spp., and evaluate the susceptibility of isolates.In this manuscript, some of the causative cryptic Aspergillus spp. are briefly reviewed. In addition, the exometabolome of Aspergillus section Fumigati is described. Finally, azole resistance of A. fumigatus is also discussed, in reference to several studies from Japan.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; Aspergillus fumigatus; Azoles; Drug Resistance, Fungal; Humans; Metabolome
PubMed: 27904060
DOI: 10.3314/mmj.16.005 -
Medical Mycology Journal 2011