The alkynyl-containing compounds from mushrooms and their biological activities.

Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties. They are a crucial natural source of bioactive secondary metabolites, and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses. Despite their relatively low abundance, naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity. Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities, including antitumor, antibacterial, antifungal, insecticidal, phototoxic, HIV-inhibitory, and immunosuppressive properties. This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities, focusing mainly on cytotoxicity and anticancer effects. This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms. Moreover, it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory.

Genomic and Metabolomic Analyses of the Medicinal Fungus Inonotus hispidus for Its Metabolite's Biosynthesis and Medicinal Application.

Inonotus hispidus mushroom is a traditional medicinal fungus with anti-cancer, antioxidation, and immunomodulatory activities, and it is used in folk medicine as a treatment for indigestion, cancer, diabetes, and gastric illnesses. Although I. hispidus is recognized as a rare edible medicinal macrofungi, its genomic sequence and biosynthesis potential of secondary metabolites have not been investigated. In this study, using Illumina NovaSeq combined with the PacBio platform, we sequenced and de novo assembled the whole genome of NPCB_001, a wild I. hispidus isolate from the Aksu area of Xinjiang Province, China. Comparative genomic and phylogenomic analyses reveal interspecific differences and evolutionary traits in the genus Inonotus. Bioinformatics analysis identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Additionally, molecular networks of metabolites exhibit differences in chemical composition and content between fruiting bodies and mycelium, as well as association clusters of related compounds. The deciphering of the genome of I. hispidus will deepen the understanding of the biosynthesis of bioactive components, open the path for future biosynthesis research, and promote the application of Inonotus in the fields of drug research and functional food manufacturing.

Research Progress on Fungal Sesterterpenoids Biosynthesis.

Sesterterpenes are 25-carbon terpenoids formed by the cyclization of dimethyl allyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) as structural units by sesterterpenes synthases. Some (not all) sesterterpenoids are modified by cytochrome P450s (CYP450s), resulting in more intricate structures. These compounds have significant physiological activities and pharmacological effects in anti-inflammatory, antibacterial, antitumour, and hypolipidemic communities. Despite being a rare class of terpenoids, sesterterpenoids derived from fungi show a wide range of structural variations. The discovered fungal sesterterpenoid synthases are composed of C-terminal prenyltransferase (PT) and N-terminal terpene synthase (TS) domains, which were given the name PTTSs. PTTSs have the capacities to catalyze chain lengthening and cyclization concurrently. This review summarizes all 52 fungal PTTSs synthases and their biosynthetic pathways involving 100 sesterterpenoids since the discovery of the first PTTSs synthase from fungi in 2013.

Bioactive components of Laetiporus species and their pharmacological effects.

Laetiporus species are brown rot fungi belonging to the order Polyporales in the division Basidiomycota. These species produce a variety of metabolites and provide a great source of natural material for the screening of medicinally active natural products or their derivatives. This review summarizes the research progress on bioactive metabolites of Laetiporus species up to April 2022, including biological macromolecules, for instance, polysaccharides and lectins, as well as 80 reported small molecule chemical components (15 sterols, 29 triterpenes, 10 sesquiterpenes, 5 polyenes, 10 volatile compounds, and 11 other compounds). These metabolites exhibit antimicrobial, anticancer, antioxidant, hepatoprotective, anti-inflammatory, and antidiabetic activities. Genome mining predicted 23 terpene synthases, 7 polyketide synthases, and 9 non-ribosomal peptide synthases involved in bioactive metabolites biosynthesis, which were analyzed by antiSMASH in L. sulphureus genome. This review will provide a basis for the biosynthesis of active components in Laetiporus species and a reference for the research of medical precursors. KEY POINTS: • The mini-review summarized 80 secondary metabolites of Laetiporus spp. • The main pharmacological activities of Laetiporus spp. were summarized. • Biosynthetic genes of terpenoids, polyketides, and non-ribosomal peptides were also summarized.

Biosynthesis of Sesquiterpenes in Basidiomycetes: A Review.

Sesquiterpenes are common small-molecule natural products with a wide range of promising applications and are biosynthesized by sesquiterpene synthase (STS). Basidiomycetes are valuable and important biological resources. To date, hundreds of related sesquiterpenoids have been discovered in basidiomycetes, and the biosynthetic pathways of some of these compounds have been elucidated. This review summarizes 122 STSs and 2 fusion enzymes STSs identified from 26 species of basidiomycetes over the past 20 years. The biological functions of enzymes and compound structures are described, and related research is discussed.

Genome sequencing of Inonotus obliquus reveals insights into candidate genes involved in secondary metabolite biosynthesis.

BACKGROUND: Inonotus obliquus is an important edible and medicinal mushroom that was shown to have many pharmacological activities in preclinical trials, including anti-inflammatory, antitumor, immunomodulatory, and antioxidant effects. However, the biosynthesis of these pharmacological components has rarely been reported. The lack of genomic information has hindered further molecular characterization of this mushroom. RESULTS: In this study, we report the genome of I. obliquus using a combined high-throughput Illumina NovaSeq with Oxford Nanopore PromethION sequencing platform. The de novo assembled 38.18 Mb I. obliquus genome was determined to harbor 12,525 predicted protein-coding genes, with 81.83% of them having detectable sequence similarities to others available in public databases. Phylogenetic analysis revealed the close evolutionary relationship of I. obliquus with Fomitiporia mediterranea and Sanghuangporus baumii in the Hymenochaetales clade. According to the distribution of reproduction-related genes, we predict that this mushroom possesses a tetrapolar heterothallic reproductive system. The I. obliquus genome was found to encode a repertoire of enzymes involved in carbohydrate metabolism, along with 135 cytochrome P450 proteins. The genome annotation revealed genes encoding key enzymes responsible for secondary metabolite biosynthesis, such as polysaccharides, polyketides, and terpenoids. Among them, we found four polyketide synthases and 20 sesquiterpenoid synthases belonging to four more types of cyclization mechanism, as well as 13 putative biosynthesis gene clusters involved in terpenoid synthesis in I. obliquus. CONCLUSIONS: To the best of our knowledge, this is the first reported genome of I. obliquus; we discussed its genome characteristics and functional annotations in detail and predicted secondary metabolic biosynthesis-related genes, which provides genomic information for future studies on its associated molecular mechanism.

Physiological mechanisms by which gypsum increases the growth and yield of Lentinula edodes.

Lentinula edodes is one of the most important commercially cultivated edible mushrooms. It is well known that gypsum (CaSO4·2H2O) supplementation in sawdust medium increases the yield of L. edodes, while the physiological mechanisms remain unclear. Our previous study showed that the acidification of the medium to pH 3.5-4.0 was essential for the growth of L. edodes. In this study, it was found that the oxalic acid excreted by L. edodes was responsible for the acidification of the medium. The biosynthesis of oxalic acid was regulated by the ambient pH and buffer capacity of the medium. To acidify the sawdust medium, the concentrations of total and soluble oxalate were 51.1 mmol/kg and 10.8 mmol/kg, respectively. However, when the concentration of soluble oxalate was 8.0 mmol/kg, the mycelial growth rate decreased by 29% compared with the control. Soluble oxalate was toxic to L. edodes, while soluble sulfate was nontoxic. CaSO4 reacted with soluble oxalate to form nontoxic insoluble CaC2O4 and the strong acid H2SO4. When the CaSO4 supplemented in sawdust medium was more than 25 mmol/kg, the soluble oxalate decreased to less than 1 mmol/kg, and the mycelial growth rate increased by 32% compared with the control. In conclusion, gypsum improved the growth and yield by relieving the toxicity of oxalate and facilitating the acidification of sawdust medium. KEY POINTS: • L. edodes excretes oxalic acid to acidify the ambient environment for growth. • Soluble oxalate is toxic to L. edodes. • Gypsum increases growth by reacting with oxalate to relieve its toxicity.