Fungi have the ability to transform organic materials into a rich and diverse set of useful products and provide distinct opportunities for tackling the urgent challenges before all humans. Fungal biotechnology can advance the transition from our petroleum-based economy into a bio-based circular economy and has the ability to sustainably produce resilient sources of food, feed, chemicals, fuels, textiles, and materials for construction, automotive and transportation industries, for furniture and beyond. Fungal biotechnology offers solutions for securing, stabilizing and enhancing the food supply for a growing human population, while simultaneously lowering greenhouse gas emissions. Fungal biotechnology has, thus, the potential to make a significant contribution to climate change mitigation and meeting the United Nation's sustainable development goals through the rational improvement of new and established fungal cell factories. The White Paper presented here is the result of the 2nd Think Tank meeting held by the EUROFUNG consortium in Berlin in October 2019. This paper highlights discussions on current opportunities and research challenges in fungal biotechnology and aims to inform scientists, educators, the general public, industrial stakeholders and policymakers about the current fungal biotech revolution.
The EUROFUNG network is a virtual centre of multidisciplinary expertise in the field of fungal biotechnology. The first academic-industry Think Tank was hosted by EUROFUNG to summarise the state of the art and future challenges in fungal biology and biotechnology in the coming decade. Currently, fungal cell factories are important for bulk manufacturing of organic acids, proteins, enzymes, secondary metabolites and active pharmaceutical ingredients in white and red biotechnology. In contrast, fungal pathogens of humans kill more people than malaria or tuberculosis. Fungi are significantly impacting on global food security, damaging global crop production, causing disease in domesticated animals, and spoiling an estimated 10 % of harvested crops. A number of challenges now need to be addressed to improve our strategies to control fungal pathogenicity and to optimise the use of fungi as sources for novel compounds and as cell factories for large scale manufacture of bio-based products. This white paper reports on the discussions of the Think Tank meeting and the suggestions made for moving fungal bio(techno)logy forward.
We conducted research on the potential impacts of fluvalinate and coumaphos on honey bee, Apis mellifera L., queen viability and health. Queens were reared in colonies that had been treated with differing amounts of both fluvalinate and coumaphos. Pre- and posttreatment samples of both wax and bees were collected from all of the colonies and analyzed for total concentrations of fluvalinate and coumaphos. All queens were measured for queen weight, ovarial weight, and number of sperm in the spermathecae. The queens treated with high doses of fluvalinate weighed significantly less than low-dose or control queens, but otherwise appeared to develop normally. The highest fluvalinate concentrations were observed in the wax and queen cells of the high-dose group. The developing queens in colonies treated with as little as one coumaphos-impregnated strip for more than 24 h suffered a high mortality rate. Several of the queens showed sublethal effects from the coumaphos, including physical abnormalities and atypical behavior. The queens exposed to coumaphos weighed significantly less and had lower ovary weights than the control group queens. The highest coumaphos concentrations were observed in the queen cells and wax of the high-dose groups.
The ergot diseases of grasses, caused by members of the genus Claviceps, have had a severe impact on human history and agriculture, causing devastating epidemics. However, ergot alkaloids, the toxic components of Claviceps sclerotia, have been used intensively (and misused) as pharmaceutical drugs, and efficient biotechnological processes have been developed for their in vitro production. Molecular genetics has provided detailed insight into the genetic basis of ergot alkaloid biosynthesis and opened up perspectives for the design of new alkaloids and the improvement of production strains; it has also revealed the refined infection strategy of this biotrophic pathogen, opening up the way for better control. Nevertheless, Claviceps remains an important pathogen worldwide, and a source for potential new drugs for central nervous system diseases.
The conidium plays a critical role in the life cycle of many filamentous fungi, being the primary means for survival under unfavorable conditions. To investigate the transcriptional changes taking place during the transition from growing hyphae to conidia in Trichoderma reesei, microarray experiments were performed. A total of 900 distinct genes were classified as differentially expressed, relative to their expression at time zero of conidiation, at least at one of the time points analyzed. The main functional categories (FunCat) overrepresented among the upregulated genes were those involving solute transport, metabolism, transcriptional regulation, secondary metabolite synthesis, lipases, proteases, and, particularly, cellulases and hemicellulases. Categories overrepresented among the downregulated genes were especially those associated with ribosomal and mitochondrial functions. The upregulation of cellulase and hemicellulase genes was dependent on the function of the positive transcriptional regulator XYR1, but XYR1 exerted no influence on conidiation itself. At least 20% of the significantly regulated genes were nonrandomly distributed within the T. reesei genome, suggesting an epigenetic component in the regulation of conidiation. The significant upregulation of cellulases and hemicellulases during this process, and thus cellulase and hemicellulase content in the spores of T. reesei, contributes to the hypothesis that the ability to hydrolyze plant biomass is a major trait of this fungus enabling it to break dormancy and reinitiate vegetative growth after a period of facing unfavorable conditions. Differentiation into a dormant resting stage (most frequently called "spores") has been developed by a broad variety of prokaryotic and eukaryotic organisms to survive long periods of environmentally unfavorable conditions (19,38). For a diverse group of fungi that includes many medically, industrially, and agriculturally important species, conidiation is also a common asexual reproductive mode and primary means for dispersion in the environment. It involves major rearrangements of many fundamental growth and cell cycle processes (including temporal and spatial regulation of gene expression, cell specialization, and intercellular communication) (13,17,37).The genetic mechanisms controlling these processes in fungi have been addressed in some detail for only two well-studied ascomycetes, Aspergillus nidulans and Neurospora crassa, which, despite displaying similar general mechanisms, revealed significant differences (2, 10, 13, 47). A common feature of fungal spores from both species, however, is their content of a high number of RNAs that can be rapidly translated at the very beginning of germination, thus minimizing the time and energy needed to initiate growth once a suitable substrate becomes available.The filamentous fungus Trichoderma reesei (the anamorph of the pantropical ascomycete Hypocrea jecorina [28]) is intensively investigated because of its ability to produce plant biomass-hydrolyzing enzyme mixtur...
Clavines and D-lysergic acid-derived alkaloid amides and alkaloid peptides are two different families of compounds that have the indole-derived tetracyclic metergoline ring system in common. Previous work has shown that D-lysergic acid is biosynthetically derived from clavine alkaloids. Recent cloning and analysis of the ergot alkaloid biosynthesis gene cluster from the D-lysergic acid peptide (ergopeptines)-producing Claviceps purpurea, has shown that it most probably contains all genes necessary for D-lysergic acid synthesis as well as those that encode the assembly of D-lysergic acid peptides, such as ergotamine. To address the role of the oxygenase genes of alkaloid-gene clusters, the only cytochrome P450 monooxygenase gene of this cluster was inactivated by disruption. The resultant mutant accumulated agroclavine, elymoclavine, and chanoclavine in substantial amounts but not ergopeptines. Feeding the mutant with D-lysergic acid restored ergopeptine synthesis; this suggests a block in the conversion of elymoclavine to D-lysergic acid. The gene was designated cloA (for encoding a clavine oxidase, CLOA). Retransformation of the mutant with the intact cloA gene also restored ergopeptine synthesis. These data show that CLOA catalyses the conversion of clavines to D-lysergic acid, it acts as a critical enzyme in the ergot alkaloid gene cluster, and bridges the biosynthesis of the two different families of alkaloids.
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