• The amazing potential of fungi: 50 ways we can exploit fungi industrially

      Hyde, Kevin D.; Xu, Jianchu; Rapior, Sylvie; Jeewon, Rajesh; Lumyong, Saisamorn; Niego, Allen Grace T.; Abeywickrama, Pranami D.; Aluthmuhandiram, Janith V.S.; Brahamanage, Rashika S.; Brooks, Siraprapa; et al. (Springer, 2019-07-31)
      Fungi are an understudied, biotechnologically valuable group of organisms. Due to the immense range of habitats that fungi inhabit, and the consequent need to compete against a diverse array of other fungi, bacteria, and animals, fungi have developed numerous survival mechanisms. The unique attributes of fungi thus herald great promise for their application in biotechnology and industry. Moreover, fungi can be grown with relative ease, making production at scale viable. The search for fungal biodiversity, and the construction of a living fungi collection, both have incredible economic potential in locating organisms with novel industrial uses that will lead to novel products. This manuscript reviews fifty ways in which fungi can potentially be utilized as biotechnology. We provide notes and examples for each potential exploitation and give examples from our own work and the work of other notable researchers. We also provide a flow chart that can be used to convince funding bodies of the importance of fungi for biotechnological research and as potential products. Fungi have provided the world with penicillin, lovastatin, and other globally significant medicines, and they remain an untapped resource with enormous industrial potential.
    • Biological and chemical diversity go hand in hand: Basidiomycota as source of new pharmaceuticals and agrochemicals.

      Sandargo, Birthe; Chepkirui, Clara; Cheng, Tian; Chaverra-Muñoz, Lillibeth; Thongbai, Benjarong; Stadler, Marc; Hüttel, Stephan; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2019-02-07)
      The Basidiomycota constitutes the second largest higher taxonomic group of the Fungi after the Ascomycota and comprises over 30.000 species. Mycelial cultures of Basidiomycota have already been studied since the 1950s for production of antibiotics and other beneficial secondary metabolites. Despite the fact that unique and selective compounds like pleuromutilin were obtained early on, it took several decades more until they were subjected to a systematic screening for antimicrobial and anticancer activities. These efforts led to the discovery of the strobilurins and several hundreds of further compounds that mainly constitute terpenoids. In parallel the traditional medicinal mushrooms of Asia were also studied intensively for metabolite production, aimed at finding new therapeutic agents for treatment of various diseases including metabolic disorders and the central nervous system. While the evaluation of this organism group has in general been more tedious as compared to the Ascomycota, the chances to discover new metabolites and to develop them further to candidates for drugs, agrochemicals and other products for the Life Science industry have substantially increased over the past decade. This is owing to the revolutionary developments in -OMICS techniques, bioinformatics, analytical chemistry and biotechnological process technology, which are steadily being developed further. On the other hand, the new developments in polythetic fungal taxonomy now also allow a more concise selection of previously untapped organisms. The current review is dedicated to summarize the state of the art and to give an outlook to further developments.
    • The Biomolecular Spectrum Drives Microbial Biology and Functions in Agri-Food-Environments.

      Sharma, Minaxi; Singh, Dhananjaya Pratap; Rangappa, Kanchugarakoppal S; Stadler, Marc; Mishra, Pradeep Kumar; Silva, Roberto Nascimento; Prasad, Ram; Gupta, Vijai Kumar; HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany. (MDPI, 2020-03-04)
      Microbial biomolecules have huge commercial and industrial potential. In nature, biological interactions are mostly associated with biochemical and biological diversity, especially with the discovery of associated biomolecules from microbes. Within cellular or subcellular systems, biomolecules signify the actual statuses of the microorganisms. Understanding the biological prospecting of the diverse microbial community and their complexities and communications with the environment forms a vital basis for active, innovative biotechnological breakthroughs. Biochemical diversity rather than the specific chemicals that has the utmost biological importance. The identification and quantification of the comprehensive biochemical diversity of the microbial molecules, which generally consequences in a diversity of biological functions, has significant biotechnological potential. Beneficial microbes and their biomolecules of interest can assist as potential constituents for the wide-range of natural product-based preparations and formulations currently being developed on an industrial scale. The understanding of the production methods and functions of these biomolecules will contribute to valorisation of agriculture, food bioprocessing and biopharma, and prevent human diseases related to the environment.
    • Diversity of Myxobacteria-We Only See the Tip of the Iceberg.

      Mohr, Kathrin I; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2018-08-11)
      The discovery of new antibiotics is mandatory with regard to the increasing number of resistant pathogens. One approach is the search for new antibiotic producers in nature. Among actinomycetes, Bacillus species, and fungi, myxobacteria have been a rich source for bioactive secondary metabolites for decades. To date, about 600 substances could be described, many of them with antibacterial, antifungal, or cytostatic activity. But, recent cultivation-independent studies on marine, terrestrial, or uncommon habitats unequivocally demonstrate that the number of uncultured myxobacteria is much higher than would be expected from the number of cultivated strains. Although several highly promising myxobacterial taxa have been identified recently, this so-called Great Plate Count Anomaly must be overcome to get broader access to new secondary metabolite producers. In the last years it turned out that especially new species, genera, and families of myxobacteria are promising sources for new bioactive metabolites. Therefore, the cultivation of the hitherto uncultivable ones is our biggest challenge.
    • Investigating the Function of Cryptic Cytochalasan Cytochrome P450 Monooxygenases Using Combinatorial Biosynthesis.

      Wang, Chongqing; Becker, Kevin; Pfütze, Sebastian; Kuhnert, Eric; Stadler, Marc; Cox, Russell J; Skellam, Elizabeth; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (ACS, 2019-10-23)
      Tailoring enzymes in cytochalasan biosynthesis are relatively promiscuous. Exploiting this property, we deduced the function of four cryptic cytochrome P450 monooxygenases via heterologous expression of six cytochrome P450-encoding genes, originating from Hypoxylon fragiforme and Pyricularia oryzae, in pyrichalasin H ΔP450 strains. Three cryptic cytochrome P450 enzymes (HffD, HffG, and CYP1) restored pyrichalasin H production in mutant strains, while CYP3 catalyzed a site-selective epoxidation leading to the isolation of three novel cytochalasans.
    • Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

      Mulwa, Lucky S.; Jansen, Rolf; Praditya, Dimas F.; Mohr, Kathrin I.; Okanya, Patrick W.; Wink, Joachim; Steinmann, Eike; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Beilstein-Institut, 2018-06-26)
      Lanyamycin (1/2), a secondary metabolite occurring as two epimers, was isolated from the myxobacterium Sorangium cellulosum, strain Soce 481. The structures of both epimers were elucidated from HRESIMS and 1D and 2D NMR data and the relative configuration of their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929 and the human nasopharyngeal cell line KB3 with IC50 values of 3.1 and 1.5 μM, respectively, and also suppressed the growth of the Gram-positive bacterium Micrococcus luteus.
    • Phylogenetic and chemotaxonomic studies confirm the affinities of Stromatoneurospora phoenix to the Coprophilous xylariaceae

      Becker, Kevin; Wongkanoun, Sarunyou; Wessel, Anna Charleen; Bills, Gerald F.; Stadler, Marc; Luangsa-ard, J. Jennifer; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2020-09-01)
      The genus Stromatoneurospora was erected in 1973 by Jong and Davis to accommodate the pyrophilic pyrenomycete Sphaeria phoenix and has traditionally been placed in the family Xylariaceae based on morphological features. However, no living culture of this genus has so far been available in the public domain. Molecular data were restricted to an internal transcribed spacer (ITS) sequence that only confirmed the familial position, and was generated from a strain that is not deposited in a public culture collection. We have recently collected fresh material and were able to culture this fungus from Thailand. The secondary metabolites of this strains were analysed after fermentation in multiple media. The the prominent components of these fermentation were purified, using preparative chromatography. Aside from two new eremophilane sesquiterpenoids named phoenixilanes A-B (1-2), four other components that are known from species of the xylariaceous genera Xylaria and Poronia were identified by spectral methods (nuclear magnetic resonance spectroscopy and high resolution mass spectrometry). Notably, (-)-(R)-6-hydroxy-3-methyl-4-dihydroisocoumarin-5-carboxylic acid (6) has not been reported as a natural product before. Moreover, DNA sequences of Stromatoneurospora phoenix clustered with members of the genera Poronia and Podosordaria in a multi-locus molecular phylogeny. These results confirmed that the genus belongs to the same evolutionary lineage as the coprophilic Xylariaceae. The results also suggest that this lineage has evolved independently from the plant-inhabiting saprotrophs and endophytes that are closely related to the genus Xylaria. These findings are discussed in relation to some theories about the endophytic vs. the pyrophilic/coprophilic fungal life style.
    • Tutuilamides A-C: Vinyl-Chloride-Containing Cyclodepsipeptides from Marine Cyanobacteria with Potent Elastase Inhibitory Properties.

      Keller, Lena; Canuto, Kirley Marques; Liu, Chenxi; Suzuki, Brian M; Almaliti, Jehad; Sikandar, Asfandyar; Naman, C Benjamin; Glukhov, Evgenia; Luo, Danmeng; Duggan, Brendan M; et al. (AmericanChemical Society(ACS), 2020-01-28)
      Marine cyanobacteria (blue-green algae) have been shown to possess an enormous capacity to produce structurally diverse natural products that exhibit a broad spectrum of potent biological activities, including cytotoxic, antifungal, antiparasitic, antiviral, and antibacterial activities. Using mass-spectrometry-guided fractionation together with molecular networking, cyanobacterial field collections from American Samoa and Palmyra Atoll yielded three new cyclic peptides, tutuilamides A-C. Their structures were established by spectroscopic techniques including 1D and 2D NMR, HR-MS, and chemical derivatization. Structure elucidation was facilitated by employing advanced NMR techniques including nonuniform sampling in combination with the 1,1-ADEQUATE experiment. These cyclic peptides are characterized by the presence of several unusual residues including 3-amino-6-hydroxy-2-piperidone and 2-amino-2-butenoic acid, together with a novel vinyl chloride-containing residue. Tutuilamides A-C show potent elastase inhibitory activity together with moderate potency in H-460 lung cancer cell cytotoxicity assays. The binding mode to elastase was analyzed by X-ray crystallography revealing a reversible binding mode similar to the natural product lyngbyastatin 7. The presence of an additional hydrogen bond with the amino acid backbone of the flexible side chain of tutuilamide A, compared to lyngbyastatin 7, facilitates its stabilization in the elastase binding pocket and possibly explains its enhanced inhibitory potency.