Recent Progress in Biodiversity Research on the Xylariales and Their Secondary Metabolism
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The Journal of Antibiotics (2021) 74:1–23 https://doi.org/10.1038/s41429-020-00376-0 SPECIAL FEATURE: REVIEW ARTICLE Recent progress in biodiversity research on the Xylariales and their secondary metabolism 1,2 1,2 Kevin Becker ● Marc Stadler Received: 22 July 2020 / Revised: 16 September 2020 / Accepted: 19 September 2020 / Published online: 23 October 2020 © The Author(s) 2020. This article is published with open access Abstract 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 fi 1234567890();,: 1234567890();,: ascomycetes, and polythetic taxonomy now allows for elucidation of the life cycle of the endophytes for the rst 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. Introduction lineages of fungi are detected [2, 3]. It often has been postulated that these unknown fungal organisms may con- Recent studies relying on bioinformatics, molecular ecol- stitute a great resource for new enzymes, drugs, agro- ogy, and phylogenetics have revealed a very high species chemicals, and other useful natural molecules, but by far not diversity in the fungal kingdom, and according to some all groups of fungi have a diverse secondary metabolism. estimates, there are several million undescribed species [1]. This has only been proven for certain taxonomic entities Recent studies using high-throughput and third generation like the order Xylariales, from which a large number of sequencing techniques are now able to depict the diversity unique carbon skeletons have already been discovered very accurately and often hitherto unknown phylogenetic during the course of classical natural product screening programmes. The current paper follows up on the review by Helaly et al. [4], where the state-of-the-art on secondary meta- This paper is dedicated to the memory of our friend and colleague, bolite discovery and various correlations to biodiversity Prof. Dr. Soleiman E. Helaly, who was the lead author of the preceding research had been described for this fungal order, taking review on the same topic and passed away much too early in June the most important papers that were published until 2017 of 2020. into account. Only 3 years later, a lot of new information * Marc Stadler has accumulated and it is already time for an update. The [email protected] present paper is roughly divided in three parts, the first two of which are dealing with interesting new compounds 1 Department Microbial Drugs, Helmholtz Centre for Infection from the two large families within Xylariales, Xylariaceae, Research GmbH, Inhoffenstraße 7, 38124 Braunschweig, Germany and Hypoxylaceae (for illustrations of representative species see Fig. 1), and the third part covers recent taxo- 2 German Centre for Infection Research Association (DZIF), partner site Hannover-Braunschweig, Inhoffenstraße 7, 38124 nomic, chemoecological, and phylogenomic studies of Braunschweig, Germany these fungi. 2 K. Becker, M. Stadler Fig. 1 Stromata of some tropical and subtropical species of Xylariales. a Xylaria melanura. b X. telfairii. c X. grammica. d Hypoxylon haematostroma. e Pyrenopolyporus hunteri. f H. griseobrunneum. Images were kindly provided by Esteban B. Sir Novel secondary metabolites from the Hypocopra and Kretzschmaria, are nearly untapped con- Xylariaceae sensu stricto (Fig. 2) cerning their secondary metabolites. This may be the case because they have rarely been collected or because they are After recent taxonomic revisions, in which other families not easy to cultivate. like the Hypoxylaceae have been excluded, and only Most of the compounds described today are still dis- counting the genera that have been studied by molecular covered by the classical method of axenic cultivation, either phylogenetic methods or examination of the asexual stages, in submerged culture or on solid media, and successive the Xylariaceae sensu strictu presently comprise 33 genera extraction. However, other approaches like biotransforma- and over 1000 (and up to 1230) species, of which more than tion, co-cultivation, epigenetic modification, and hetero- 50% belong to the genus Xylaria [5, 6]. The number of logous expression are encountered occasionally and will be accepted Xylaria taxa vary from 570 to 670 in these recent discussed herein as well. overviews, depending on whether synonyms and variations Subsequently, the genera for which novel secondary are counted. The genus Xylaria has never been subjected to metabolites have been described in the past 3 years will be a world monograph using modern, polythetic methodology. dealt with, and secondary metabolites by their affiliation to From the outcome of such work in other genera of the different compound classes. Some papers published prior to Xylariales, it is possible that Xylaria actually comprises 2018 will be included herein for the sake of integrity in several thousands of species of which the majority remains concurrence with the latest review [4], which covers most of to be recognized and formally described [7]. the literature on secondary metabolites from Xylariales up For this reason, it is not surprising that most of the new to the end of 2017. We preferentially treat compounds that metabolites reported from the family were derived from were not already reported previously [4, 9, 10]. Xylaria species, as highlighted in a comprehensive review The genus Amphirosellinia was not studied for second- some years ago [4], for which we provide an update from ary metabolites until recently, when the first natural product, the past years. It is important to note that most of the coriloxin (1), was discovered from cultures of Amphir- metabolites of Xylaria reported over the past decade have osellinia nigrospora [11]. Coriloxin represents a known actually been isolated from endophytic strains. cyclohexenone derivative [12] and was found to have weak Besides Xylaria, only for some genera of the Xylariaceae antimicrobial activities. However, the crude extract of the novel secondary metabolites have been described in the past fungus showed stronger bioactivities than the purified 3 years. Those included Nemania, Rosellinia, and Dema- compound against phytopathogenic bacteria like Ralstonia tophora, the latter of which has recently been resurrected solanacearum and plant-pathogenic fungi like Magna- and emended [8]. Most other genera, even larger ones like porthe oryzae, suggesting either the presence of additional Recent progress in biodiversity research on the Xylariales and their secondary metabolism 3 Fig. 2 Secondary metabolites recently described from the genera Amphirosellinia, Ascotricha, Dematophora, Nemania, and Stromatoneurospora bioactive compounds in the extract and/or synergistic (previously known as R. bunodes) named dematophoranes effects of 1 with other components. Those results render the A(3) and B. The compounds showed weak antibacterial producing organism A. nigrospora an interesting target for activity against Bacillus subtilis and Staphylococcus aureus further research on its biocontrol capabilities against crop and weak cytotoxic activities against mouse fibroblasts (cell diseases. line L929) and cervix carcinoma cells (KB 3.1). Other Ascotricha was already described to produce orsellinic purified but known isopimarenes like myrocin B and the acid-glucosides in 2017, where short-time cultivation of a glucoside hymatoxin K were already reported from other sea mud-derived Ascotricha sp. in submerged media led to species of Xylariales and Hypocreales. In addition, the isolation of two glucosides comprised of orsellinic acid and presence of additional compounds with MS data that could D-threitol, e.g.(2R,3R)-1,2,3,4-butanetetraol-1,4-diorselli- not be matched to the entries in the available natural product nate (2)[13]. For 2, even a synthesis was described shortly databases was observed, making Dematophora spp. a after [14]. No biological activities were reported for those worthwhile genus to examine more thoroughly. compounds from Ascotricha; however, they represent the Nemania is one of the largest genera in the Xylariaceae first natural products from a genus that is otherwise still and some of its species are relatively well-studied. Recently, untapped. an endopyhtic isolate named Nemania bipapillata isolated Species of Dematophora were up to recently included in from a red alga was described to produce botryane-type the genus Rosellinia, but were segregated due to differing sesquiterpenoids [15]. This class of compounds had so far asexual morphs and a well-defined clade