Many fungi, lichens, and bacteria produce xanthones (derivatives of 9H-xanthen-9-one, “xanthone” from the Greek “xanthos”, for “yellow”) as secondary metabolites. Xanthones are typically polysubstituted and occur as either fully aromatized, dihydro-, tetrahydro-, or, more rarely, hexahydro-derivatives. This family of compounds appeals to medicinal chemists because of their pronounced biological activity within a notably broad spectrum of disease states, a result of their interaction with a correspondingly diverse range of target biomolecules. This has led to the description of xanthones as “privileged structures”.(1) Historically, the total synthesis of the natural products has mostly been limited to fully aromatized targets. Syntheses of the more challenging partially saturated xanthones have less frequently been reported, although the development in recent times of novel and reliable methods for the construction of the (polysubstituted) unsaturated xanthone core holds promise for future endeavors. In particular, the fascinating structural and biological properties of xanthone dimers and heterodimers may excite the synthetic or natural product chemist.

Xanthones from fungi, lichens, and bacteria : the natural products and their synthesis

Artemisinin, a miracle of traditional Chinese medicine

Diversity and taxonomy of Chaetomium and chaetomium-like fungi from indoor environments

Chaetomium globosum, the type species of the genus, is ubiquitous, occurring on a wide variety of substrates, in air and in marine environments. This species is recognised as a cellulolytic and/or endophytic fungus. It is also known as a source of secondary metabolites with various biological activities, having great potential in the agricultural, medicinal and industrial fields. On the negative side, C. globosum has been reported as an air contaminant causing adverse health effects and as causal agent of human fungal infections. However, the taxonomic status of C. globosum is still poorly understood. The contemporary species concept for this fungus includes a broadly defined morphological diversity as well as a large number of synonymies with limited phylogenetic evidence. The aim of this study is, therefore, to resolve the phylogenetic limits of C. globosum s.str. and related species. Screening of isolates in the collections of the CBS-KNAW Fungal Biodiversity Centre (The Netherlands) and the China General Microbiological Culture Collection Centre (China) resulted in recognising 80 representative isolates of the C. globosum species complex. Thirty-six species are identified based on phylogenetic inference of six loci, supported by typical morphological characters, mainly ascospore shape. Of these, 12 species are newly described here. Additionally, C. cruentum, C. mollipilium, C. rectum, C. subterraneum and two varieties of C. globosum are synonymised under C. globosum s.str., and six species are resurrected, i.e. C. angustispirale, C. coarctatum, C. cochliodes, C. olivaceum, C. spiculipilium and C. subglobosum. Chaetomium ascotrichoides is segregated from C. madrasense and the genus name Chaetomidium is rejected. Five species, including C. globosum s.str., are typified here to stabilise their taxonomic status. A further evaluation of the six loci used in this study as potential barcodes indicated that the 28S large subunit (LSU) nrDNA and the internal transcribed spacer regions and intervening 5.8S nrRNA (ITS) gene regions were unreliable to resolve species, whereas β-tubulin (tub2) and RNA polymerase II second largest subunit (rpb2) showed the greatest promise as DNA barcodes for differentiating Chaetomium species. This study provides a starting point to establish a more robust classification system for Chaetomium and for the Chaetomiaceae.

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Phylogenetic reassessment of the Chaetomium globosum species complex

Interaction between gut microbiota and ethnomedicine constituents.

The Pictet–Spengler (PS) reaction constructs plant alkaloids such as morphine and camptothecin, but it has not yet been noticed in the fungal kingdom. Here, a silent fungal Pictet–Spenglerase (FPS) gene of Chaetomium globosum 1C51 residing in Epinephelus drummondhayi guts is described and ascertained to be activable by 1-methyl-l-tryptophan (1-MT). The activated FPS expression enables the PS reaction between 1-MT and flavipin (fungal aldehyde) to form “unnatural” natural products with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase. A gene-implied enzyme inhibition (GIEI) strategy has been introduced to address the key steps for PS product diversifications. In aggregation, the work designs and validates an innovative approach that can activate the PS reaction-based fungal biosynthetic machinery to produce unpredictable compounds of unusual and novel structure valuable for new biology and biomedicine.

https://www.pnas.org/content/pnas/111/51/18138.full.pdf

Pictet–Spengler reaction-based biosynthetic machinery in fungi

The mangrove-derived endophytic fungus Peniophora incarnata Z4 produced seven new xanthone derivatives, including four new tetrahydroxanthones (1-4), one new chromone (5), one new xanthone (6), and one new xanthone dimer (7), together with one known compound, globosuxanthone B (8). Their structures were determined by an extensive analysis of 1D and 2D NMR, HRESIMS, ECD, and single-crystal X-ray diffraction data. In cytotoxic activity assays, compound 2 showed cytotoxicity against three carcinoma cell lines with IC50 values less than 10 μM.

Sui Jun Li

Papers

Pictet–Spengler reaction-based biosynthetic machinery in fungi

Cytotoxic Xanthone Derivatives from the Mangrove-Derived Endophytic Fungus Peniophora incarnata Z4.

New antibacterial depsidones from an ant-derived fungus Spiromastix sp. MY-1.