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.
Covering: up to December 2017 The diversity of secondary metabolites in the fungal order Xylariales is reviewed with special emphasis on correlations between chemical diversity and biodiversity as ...inferred from recent taxonomic and phylogenetic studies. The Xylariales are arguably among the predominant fungal endophytes, which are the producer organisms of pharmaceutical lead compounds including the antimycotic sordarins and the antiparasitic nodulisporic acids, as well as the marketed drug, emodepside. Many Xylariales are "macromycetes", which form conspicuous fruiting bodies (stromata), and the metabolite profiles that are predominant in the stromata are often complementary to those encountered in corresponding mycelial cultures of a given species. Secondary metabolite profiles have recently been proven highly informative as additional parameters to support classical morphology and molecular phylogenetic approaches in order to reconstruct evolutionary relationships among these fungi. Even the recent taxonomic rearrangement of the Xylariales has been relying on such approaches, since certain groups of metabolites seem to have significance at the species, genus or family level, respectively, while others are only produced in certain taxa and their production is highly dependent on the culture conditions. The vast metabolic diversity that may be encountered in a single species or strain is illustrated based on examples like Daldinia eschscholtzii, Hypoxylon rickii, and Pestalotiopsis fici. In the future, it appears feasible to increase our knowledge of secondary metabolite diversity by embarking on certain genera that have so far been neglected, as well as by studying the volatile secondary metabolites more intensively. Methods of bioinformatics, phylogenomics and transcriptomics, which have been developed to study other fungi, are readily available for use in such scenarios.
The global bio-diversity of fungi has been extensively investigated and their species number has been estimated. Notably, the development of molecular phylogeny has revealed an unexpected fungal ...diversity and utilisation of culture-independent approaches including high-throughput amplicon sequencing has dramatically increased number of fungal operational taxonomic units. A number of novel taxa including new divisions, classes, orders and new families have been established in last decade. Many cryptic species were identified by molecular phylogeny. Based on recently generated data from culture-dependent and -independent survey on same samples, the fungal species on the earth were estimated to be 12 (11.7-13.2) million compared to 2.2-3.8 million species recently estimated by a variety of the estimation techniques. Moreover, it has been speculated that the current use of high-throughput sequencing techniques would reveal an even higher diversity than our current estimation. Recently, the formal classification of environmental sequences and permission of DNA sequence data as fungal names' type were proposed but strongly objected by the mycologist community. Surveys on fungi in unusual niches have indicated that many previously regarded "unculturable fungi" could be cultured on certain substrates under specific conditions. Moreover, the high-throughput amplicon sequencing, shotgun metagenomics and a single-cell genomics could be a powerful means to detect novel taxa. Here, we propose to separate the fungal types into physical type based on specimen, genome DNA (gDNA) type based on complete genome sequence of culturable and uncluturable fungal specimen and digital type based on environmental DNA sequence data. The physical and gDNA type should have priority, while the digital type can be temporal supplementary before the physical type and gDNA type being available. The fungal name based on the "digital type" could be assigned as the "clade" name + species name. The "clade" name could be the name of genus, family or order, etc. which the sequence of digital type affiliates to. Facilitating future cultivation efforts should be encouraged. Also, with the advancement in knowledge of fungi inhabiting various environments mostly because of rapid development of new detection technologies, more information should be expected for fungal diversity on our planet.
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 literature on biologically active secondary metabolites from Basidiomycota is reviewed and some highlights are presented•Selected examples of developmental candidates for pharmaceutial and agrochemical applications are discussed•The state of the art on biosynthesis and biotechnological production of metabolites from Basidiomycota is also discussed
In the search for novel anti-infectives from natural sources, fungi, in particular basidiomycetes, have proven to still harbor so much potential in terms of secondary metabolites diversity. There ...have been numerous reports on isolating numerous secondary metabolites from genus
. This study reports on two new triterpenoids, laetiporins C and D, and four known triterpenes from the fruiting body of
.
. The structures of the isolated compounds were elucidated based on their 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data in combination with high-resolution electrospray mass spectrometric (HR-ESIMS) data. Laetiporin C exhibited weak antifungal activity against
Furthermore, the compounds showed weak antiproliferative activity against the mouse fibroblast L929 and human cancer cell lines, including KB-3-1, A431, MCF-7, PC-3 and A549.
The taxonomic and nomenclatural history of the genus
Ganoderma
and related basidiomycetes is reviewed and compared to recent studies on its molecular phylogeny. A basidiomycete belonging to the genus
...Ganoderma
can often rather easily be recognised in the field from the macro-morphological characters of the sporocarp. The most important species and lineages can also be discriminated well by molecular phylogeny. However, the application of incongruent species concepts and the frequent misapplication of European names by chemists and other non-taxonomists have created confusion in the scientific literature. The identity of the species reported in the course of mycochemical studies can often not be verified, since no voucher material was retained. In this review, an overview on the most important types of specific chemotaxonomic traits (i.e., secondary metabolites of the basidiomes and mycelia) reported from the genus is provided. Albeit certain triterpenoids such as ganoderic and lucidenic acids, steroids (e.g. ergosterol) and triterpenes (e.g. friedelin) appear to have some chemotaxonomic value at the generic rank, their relevance for species discrimination remains to be assessed. We propose that all important names in
Ganoderma
should be, as required, epitypified by fresh collections for which living cultures should be made available and that these should be examined by a combination of morphological, chemotaxonomic and molecular phylogenetic methods to attain a more stable taxonomy.
The synthesis of a novel disorazole C1 analogue is described, and its biological activity as a cytotoxic compound is reported. Based on our convergent and flexible route to the disorazole core, we ...wish to report a robust strategy to synthesize a non-symmetrical disorazole in which we couple one half of the molecule containing the naturally occurring oxazole heterocycle and the second half of the disorazole macrocycle containing a thiazole heterocycle. This resulted in a very unusual non-symmetrical disorazole C1 analogue containing two different heterocycles, and its biological activity was studied. This provided exciting information about SAR (structure-activity-relationship) for this highly potent class of antitumor compounds.
The development of new antibiotics faces a severe crisis inter alia owing to a lack of innovative chemical scaffolds with activities against Gram‐negative and multiresistant pathogens. Herein, we ...report highly potent novel antibacterial compounds, the myxobacteria‐derived cystobactamids 1–3, which were isolated from Cystobacter sp. and show minimum inhibitory concentrations in the low μg mL−1 range. We describe the isolation and structure elucidation of three congeners as well as the identification and annotation of their biosynthetic gene cluster. By studying the self‐resistance mechanism in the natural producer organism, the molecular targets were identified as bacterial type IIa topoisomerases. As quinolones are largely exhausted as a template for new type II topoisomerase inhibitors, the cystobactamids offer exciting alternatives to generate novel antibiotics using medicinal chemistry and biosynthetic engineering.
Against multidrug resistance: A novel chemical scaffold with very pronounced activity against bacterial topoisomerases has been isolated from myxobacteria. Cystobactamid 919‐2, as the most active derivative, is a potent antibacterial agent against numerous pathogens, including some Gram‐negative species, such as E. coli and A. baumannii (see Scheme; rel and SC denote relaxed and supercoiled E. coli DNA, respectively).
sp. M2 has been isolated from a soil sample collected at the Wadden Sea beach in our ongoing program aimed at the isolation of rare Actinobacteria, ultimately targeting the discovery of new ...antibiotics. Because crude extracts derived from cultures of this strain showed inhibitory activity against the indicator organism
, it was selected for further analysis. HPLC-MS analysis of its culture broth revealed the presence of lipophilic metabolites. The two major metabolites of those were isolated by preparative reversed-phase HPLC and preparative TLC. Their planar structures were elucidated using high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D NMR data as new thiopeptide antibiotics and named litoralimycin A (
) and B (
). Although rotating frame nuclear Overhauser effect spectroscopy (ROESY) data established a Z configuration of the Δ
double bond, the stereochemistry of C-5 and C-15 were assigned as S by Marfey's method after ozonolysis. The biological activity spectrum of
and
is highly uncommon for thiopeptide antibiotics, since they showed only insignificant antibacterial activity, but
showed strong cytotoxic effects.
Eight previously undescribed compounds were isolated and characterised from the supernatant and mycelium of a culture of the basidiomycete Favolaschia calocera originating from Kakamega equatorial ...rainforest in Kenya. These were: 9- oxostrobilurins A, G, K and I and the four monochlorinated calocerins A, B, C and D. The calocerins extend our knowledge of halogenated compounds obtained from natural sources. Four further known compounds were also identified: strobilurin G, favolon, pterulinic acid and 2,3 -dihydro-1-benzoxepin derivative. The four oxostrobilurins exhibited prominent antifungal and cytotoxic activities while the four calocerins only showed cytotoxic activity.
Bioassay-guided fractionation of the supernatant and mycelium crude extracts from culture Favolaschia calocera led to the isolation of four strobilurin derivatives together with calocerin A-D. Display omitted
•Eight previously undescribed compounds were isolated from Favolaschia calocera.•Four previously undescribed strobilurin derivatives together with monochlorinated calocerins A-D were isolated.•The strobilurin derivative showed selective antifungal activity.•All isolated compounds exhibited cytotoxicity activity.
PDF
