• 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.
    • Discovery of novel biologically active secondary metabolites from Thai mycodiversity with anti-infective potential

      Kuephadungphan, Wilawan; Macabeo, Allan Patrick G.; Luangsa-Ard, Janet Jennifer; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2021-01-01)
      This mini-review is dedicated to the summary of results of the EU-funded Project “Golden Mycological Triangle” (acronym GoMyTri), which was carried out in collaboration of three research infrastructures in Germany, the Netherlands and Thailand during the years 2014–2018. The cooperation explored the mycological and microbiological biodiversity of Europe and Southeast Asia with regard to the search for the badly needed new antibiotics and other biologically active secondary metabolites. The project was conducted to foster international collaboration networks, know-how exchange and interdisciplinary training of young scientists. The first two years of the project were mainly dedicated to field work, and several hundreds of fungal cultures have been isolated from material mostly collected in Thailand. These fungal strains were characterized by morphological and molecular phylogenetic methods and several new taxa were discovered. The cultures underwent screening for antimicrobial and nematicidal metabolites and a number of bioactive metabolites have already been found, isolated and characterized. Several large phylogenetic studies have already been published that resulted from the project work. The results were also brought to the attention of the scientific community as well as the general public through various dissemination events. Based on the tremendous success of this project, a follow-up project application including additional partners from Africa and further European countries has recently been filed and approved, and the international, interdisciplinary collaboration will now continue in the new RISE-MSCA-Project (acronym “Mycobiomics”).
    • 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.
    • Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology.

      Nazir, Mamona; Saleem, Muhammad; Tousif, Muhammad Imran; Anwar, Muhammad Aijaz; Surup, Frank; Ali, Iftikhar; Wang, Daijie; Mamadalieva, Nilufar Z; Alshammari, Elham; Ashour, Mohamed L; et al. (MDPI, 2021-06-29)
      Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.
    • Natural products in drug discovery: advances and opportunities.

      Atanasov, Atanas G; Zotchev, Sergey B; Dirsch, Verena M; Supuran, Claudiu T; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.; HIPS, Helmholtz-Institut für Pharmazeutische Forschung Saarland, Universitätscampus E8.1 66123 Saarbrücken, Germany. (Springer Nature, 2021-01-28)
      Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.
    • Recent progress in biodiversity research on the Xylariales and their secondary metabolism.

      Becker, Kevin; Stadler, Marc; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer Nature, 2020-10-23)
      The 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.
    • Taxonomy, Diversity and Cultivation of the Oudemansielloid/Xeruloid Taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula and with Respect to Their Bioactivities: A Review.

      Niego, Allen Grace; Raspé, Olivier; Thongklang, Naritsada; Charoensup, Rawiwan; Lumyong, Saisamorn; Stadler, Marc; Hyde, Kevin D; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (MDPI, 2021-01-13)
      The oudemansielloid/xeruloid taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula are genera of Basidiomycota that constitute an important resource of bioactive compounds. Numerous studies have shown antimicrobial, anti-oxidative, anti-cancer, anti-inflammatory and other bioactivities of their extracts. The bioactive principles can be divided into two major groups: (a) hydrophilic polysaccharides with relatively high molecular weights and (b) low molecular medium polar secondary metabolites, such as the antifungal strobilurins. In this review, we summarize the state of the art on biodiversity, cultivation of the fungi and bioactivities of their secondary metabolites and discuss future applications. Although the strobilurins are well-documented, with commercial applications as agrochemical fungicides, there are also other known compounds from this group that have not yet been well-studied. Polysaccharides, dihydro-citrinone phenol A acid, scalusamides, and acetylenic lactones such as xerulin, also have potential applications in the nutraceutical, pharmaceutical and medicinal market and should be further explored. Further studies are recommended to isolate high quality bioactive compounds and fully understand their modes of action. Given that only few species of oudemansielloid/xeruloid mushrooms have been explored for their production of secondary metabolites, these taxa represent unexplored sources of potentially useful and novel bioactive metabolites.