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Sarcodon mushrooms are esteemed as a rare and highly valuable resource for both culinary and medicinal purposes. Ancient medical classics have documented their beneficial effects on conditions such as indigestion, loss of appetite, and neurological disorders. Modern phytochemical research into their secondary metabolites has led to the discovery of numerous bioactive compounds with significant biological activities. Despite notable achievements in the study of the chemical composition and bioactivity of Sarcodon mushrooms, a comprehensive understanding of these findings has been lacking. This review provides an exhaustive summary of the advancements in the phytochemistry of Sarcodon mushrooms, as well as the biological and pharmacological activities of the isolated compounds and crude extracts derived from Sarcodon over the past nine decades. A total of 100 secondary metabolites isolated from these mushrooms have been classified into five major categories based on their chemical structures, which exhibit bioactivities such as anti-tumour, neurotrophic, and neuroprotective, antioxidant, anti-inflammatory, antimicrobial, and hypoglycaemic properties. The aim of this study is to establish a scientific foundation for future research in drug discovery, biotechnological development, and the exploration of functional foods involving Sarcodon mushrooms.

The family Diatrypaceae is a less well-known group within the order Xylariales (Ascomycota). Initially, the focus on its metabolites was related to the pathogenicity of one of its members, Eutypa lata. To date, a total of 254 natural products have been identified from Diatrypaceae strains. These compounds include terpenoids, sterols, polyketones, phenols, and acetylene aromatic compounds, which have shown anticancer, cytotoxic, anti-inflammatory, antimicrobial, and antiviral activities. The complex and diverse structural types, along with the diverse bioactivities, highlight the potential of Diatrypaceae as a valuable source of bioactive natural products. In this review, a deep analysis of the biosynthesis of pimarane diterpenes and scoparasin-type cytochalasins is provided, coupled with a compilation of the biosynthetic pathways of aromatic acetylene compounds in filamentous fungi. This comprehensive review not only enhances our understanding of the natural product chemistry, biological activities, and biosynthesis of secondary metabolites from the Diatrypaceae family but also promotes the exploitation and development of important bioactive compounds and potential strains.

Abstract Cyathus olla, belonging to the genus Cyathus within the order Agaricales, is renowned for its bird's nest-like fruiting bodies and has been utilized in folk medicine. However, its genome remains poorly understood. To investigate genomic diversity within the genus Cyathus and elucidate biosynthetic pathways for medicinal compounds, we generated a high-quality genome assembly of C. olla with fourteen chromosomes. The comparative genome analysis revealed variations in both genomes and specific functional genes within the genus Cyathus. Phylogenomic and gene family variation analyses provided insights into evolutionary divergence, as well as genome expansion and contraction in individual Cyathus species and 36 typical Basidiomycota. Furthermore, analysis of LTR-RT and Ka/Ks revealed apparent whole-genome duplication (WGD) events its genome. Through genome mining and metabolite profiling, we identified the biosynthetic gene cluster (BGC) for cyathane diterpenes from C. olla. Furthermore, we predicted 32 BGCs, containing 41 core genes, involved in other bioactive metabolites. These findings represent a valuable genomic resource that will enhance our understanding of Cyathus species genetic diversity. The genome analysis of C. olla provides insights into the biosynthesis of medicinal compounds and establishes a fundamental basis for future investigations into the genetic basis of chemodiversity in this significant medicinal fungus.

Abstract Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products. Glucosylation is the most common type of glycosylation, whereas xylosylation is relatively rare. Despite their unique chemical structures and beneficial activities, xylosylated natural products from microorganisms have received little attention. This review provides, for the first time, a comprehensive summary of 126 microbial-derived xylosylated natural products, including xylosyl-cyathane diterpenes, xylosylated triterpenes, xylosyl aromatic compounds, and others. Among these compounds, xylosyl-cyathane diterpenes represent the highest number of derivatives, followed by xylosylated triterpenes. Xylosyl compounds from bacterial sources have less defined structural profiles compared to those from fungi. The characterization of xylosyltransferase EriJ from Basidiomycota extended the structural diversity of xylosyl cyathane diterpenes. This work provides a valuable reference for the research and use of xylosyltransferase for drug discovery and synthetic chemistry. Further work is needed to explore the potential applications of microbial derived xylosyl compounds and to develop novel xylosyl transferases. With the deepening of genomic sequencing of medicinal fungi, more biosynthesis of bioactive xylosyl compounds is expected to be elucidated in the future. Graphical Abstract

Abstract 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. Graphical Abstract

Abstract Background Artemisiae Scopariae Herba (ASH) has been widely used as plant medicine in East Asia with remarkable antitumor activity. However, the underlying mechanisms have not been fully elucidated. Methods This study aimed to construct a multi-disciplinary approach to screen topoisomerase I (topo I) inhibitors from ASH extract, and explore the antitumor mechanisms. Bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS was used to identify chemical constitution of ASH extract as well as the topo I inhibitors, and in silico docking coupled with multiple complex networks was applied to interpret the molecular mechanisms. Results Crude ASH extract exhibited toxicogenetic and antiproliferative activities on A549 cells. A series of 34 ingredients were identified from the extract, and 6 compounds were screened as potential topo I inhibitors. Docking results showed that the formation of hydrogen bond and π-π stacking contributed most to their binding with topo I. Interrelationships among the 6 compounds, related targets and pathways were analyzed by multiple complex networks model. These networks displayed power-law degree distribution and small-world property. Statistical analysis indicated that isorhamnetin and quercetin were main active ingredients, and that chemical carcinogenesis-reactive oxygen species was the critical pathway. Electrophoretic results showed a therapeutic effect of ASH extract on the conversion of supercoiled DNA to relaxed forms, as well as potential synergistic effect of isorhamnetin and quercetin. Conclusions The results improved current understanding of Artemisiae Scopariae Herba on the treatment of tumor. Moreover, the combination of multi-disciplinary methods provided a new strategy for the study of bioactive constituents in medicinal plants.

Abstract Background Orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid, OA) and its structural analog o-Orsellinaldehyde, have become widely used intermediates in clinical drugs synthesis. Although the research on the biosynthesis of such compounds has made significant progress, due to the lack of suitable hosts, there is still far from the industrial production of such compounds based on synthetic biology. Results With the help of genome mining, we found a polyketide synthase (PKS, HerA) in the genome of the Hericium erinaceus, which shares 60% amino acid sequence homology with ArmB from Armillaria mellea, an identified PKS capable of synthesizing OA. To characterize the function of HerA, we cloned herA and heterologously expressed it in Aspergillus oryzae, and successfully detected the production of OA. Subsequently, the introduction of an incomplete PKS (Pks5) from Ustilago maydis containing only three domains (AMP-ACP-R), which was into herA-containing A. oryzae, the resulted in the production of o-Orsellinaldehyde. Considering the economic value of OA and o-Orsellinaldehyde, we then optimized the yield of these compounds in A. oryzae. The screening showed that when maltose was used as carbon source, the yields of OA and o-Orsellinaldehyde were 57.68 mg/L and 15.71 mg/L respectively, while the yields were 340.41 mg/Kg and 84.79 mg/Kg respectively in rice medium for 10 days. Conclusions Herein, we successfully expressed the genes of basidiomycetes using A. oryzae heterologous host. As a fungus of ascomycetes, which not only correctly splices genes of basidiomycetes containing multiple introns, but also efficiently produces their metabolites. This study highlights that A. oryzae is an excellent host for the heterologous production of fungal natural products, and has the potential to become an efficient chassis for the production of basidiomycete secondary metabolites in synthetic biology. Graphical Abstract

Cordyceps sinensis is a precious medicinal and edible fungus, which is widely used in body health care and disease prevention. The current research focuses on the comparison of metabolite characteristics between a small number of samples and lacks a comprehensive evaluation of the quality of C. sinensis in a large-scale space. In this study, LC-MS/MS, principal component analysis (PCA), hierarchical cluster analysis (HCA), and the membership function method were used to comprehensively evaluate the characteristics and quality of metabolites in 15 main producing areas of C. sinensis in China. The results showed that a total of 130 categories, 14 supercategories, and 1718 metabolites were identified. Carboxylic acids and derivatives, fatty acyls, organo-oxygen compounds, benzene and substituted derivatives, prenol lipids, and glycerophospholipids were the main components of C. sinensis. The HCA analysis and KEGG pathway enrichment analysis of 559 differentially accumulated metabolites (DAMs) showed that the accumulation models of fatty acids and conjugates and carbohydrates and carbohydrate conjugates in glycerophospholipid metabolism and arginine and proline metabolism may be one of the reasons for the quality differences in C. sinensis in different producing areas. In addition, a total of 18 biomarkers were identified and validated, which had a significant discrimination effect on the samples (p < 0.05). Overall, YS, BR, and ZD, with the highest membership function values, are rich and balanced in nutrients. They are excellent raw materials for the development of functional foods and provide scientific guidance for consumers to nourish health care.

Abstract Indole diterpenoids (IDTs) are an essential class of structurally diverse fungal secondary metabolites, that generally appear to be restricted to a limited number of fungi, such as Penicillium, Aspergillus, Claviceps, and Epichloe species, etc. These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphosphate (GGPP) and an indole ring moiety derived from indole-3-glycerol phosphate (IGP). 3-geranylgeranylindole (3-GGI) is the common precursor of all IDTs. On this basis, it is modified by cyclization, oxidation, and prenylation to generate a large class of compounds with complex structures. These compounds exhibit antibacterial, anti-insect, and ion channel inhibitory activities. We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years, these compounds were reclassified, and their biological activities were summarized. This review will help to understand the structural diversity of IDTs and provide help for their physiological activities. Graphical Abstract

TRPCs, nonselective cation channels, are involved in cardiac contraction and conduction. Here, the authors show that Trpc1/6 deficiency or pharmacological inhibition improves endotoxemic cardiac dysfunction and prolongs survival by prominently suppressing cardiac inflammation and ER Ca2+ release.

Piericidins are a large family of bacterial α-pyridone antibiotics with antitumor activities such as their anti-renal carcinoma activity exhibited recently in nude mice. The backbones of piericidins are derived from β, δ-diketo carboxylic acids, which are offloaded from a modular polyketide synthase (PKS) and putatively undergo a carbonyl amidation before α-pyridone ring formation. The tailoring modifications to the α-pyridone structure mainly include the verified hydroxylation and O-methylation of the C-4′ position and an unidentified C-5′ O-methylation. Here, we describe a piericidin producer, terrestrial Streptomyces conglobatus, which contains a piericidin biosynthetic gene cluster in two different loci. Deletion of the amidotransferase gene pieD resulted in the accumulation of two fatty acids that should be degraded from the nascent carboxylic acid released by the PKS, supporting the carbonyl amidation function of PieD during α-pyridone ring formation. Deletion of the O-methyltransferase gene pieB1 led to the production of three piericidin analogues lacking C-5′ O-methylation, therefore confirming that PieB1 specifically catalyses the tailoring modification. Moreover, bioactivity analysis of the mutant-derived products provided clues regarding the structure-function relationship for antitumor activity. The work addresses two previously unidentified steps involved in pyridyl pharmacophore formation during piericidin biosynthesis, facilitating the rational bioengineering of the biosynthetic pathway towards valuable antitumor agents.

Fresh and dried Cordyceps sinensis are widely used by the public for medicinal and health purposes. However, the differences between them have not been examined. In this study, fresh wild and artificial C. sinensis (WFC and AFC) were dried to obtain dried wild and artificial C. sinensis (WDC and ADC). Non-targeted GC-MS was used to analyze the metabolic profile characteristics of the four groups of samples. The results showed that air drying significantly altered the composition and content of C. sinensis, mainly in the form of higher abundance of organic acids and derivatives and lower abundance of lipids and lipid-like molecules in fresh C. sinensis. Hierarchical cluster analysis (HCA) and quantitative analyses showed that air drying increased the abundance of Valine, Zinniol, Urocanate, Vulpinic acid, and Uridine 5’-diphosphate, and decreased Xanthotoxol, Vitexin-4-o-glucoside, Val-trp, and Wogonin. These differentially accumulated metabolites (DAMs) were also shown to be potential biomarkers for C. sinensis. KEGG enrichment analysis identified lysine biosynthesis as the most significantly enriched pathway. Annotation of these DAMs to lysine biosynthesis revealed that citrate cycle and pyruvate metabolism entered lysine biosynthesis via 2-oxohlutarate and Homocitrate, respectively, resulting in significant enrichment of L-saccharopine and L-lysine content was significantly higher. Alanine, aspartate, and Glutamate metabolism synthesized more L-aspartate to promote L-lysine synthesis. Thus, high levels of L-lysine result in lysine degradation and pymolysine, which are the most active metabolic pathways during the drying of fresh C. sinensis and indirectly lead to differences in metabolic profiles.

Abstract Background Cyclic dipeptides are an important class of natural products owing to their structural diversity and biological activities. In fungi, the cyclo-ring system is formed through the condensation of two α-amino acids via non-ribosomal peptide synthetase (NRPS). However, there are few investigations on the functional identification of this enzyme. Additionally, information on how to increase the production of cyclic dipeptide molecules is relatively scarce. Results We isolated the Eurotium cristatum NWAFU-1 fungus from Jing-Wei Fu brick tea, whose fermentation metabolites contain echinulin-related cyclic dipeptide molecules. We cloned the cirC gene, encoding an NRPS, from E. Cristatum NWAFU-1 and transferred it into the heterologous host Aspergillus oryzae. This transformant produced a novel metabolite possessing an l-tryptophan-l-alanine cyclic dipeptide backbone (Cyclo-TA). Based on the results of heterologous expression and microsomal catalysis, CriC is the first NRPS characterized in fungi that catalyzes the formation of a cyclic dipeptide from l-tryptophan and l-alanine. After substrate feeding, the final yield reached 34 mg/L. In this study, we have characterized a novel NRPS and developed a new method for cyclic dipeptide production. Conclusions In this study we successfully expressed the E. Cristatum NWAFU-1 criC gene in A. oryzae to efficiently produce cyclic dipeptide compounds. Our findings indicate that the A. oryzae heterologous expression system constitutes an efficient method for the biosynthesis of fungal Cyclic dipeptides.

Abstract 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.

Hericium rajendrae is an emerging species in the genus Hericium with few members. Despite being highly regarded due to its rarity, knowledge about H. rajendrae remains limited. In this study, we sequenced, de novo assembled, and annotated the complete genome of H. rajendrae NPCB A08, isolated from the Qinling Mountains in Shaanxi, China, using the Illumina NovaSeq and Nanopore PromethION technologies. Comparative genomic analysis revealed similarities and differences among the genomes of H. rajendrae, H. erinaceus, and H. coralloides. Phylogenomic analysis revealed the divergence time of the Hericium genus, while transposon analysis revealed evolutionary characteristics of the genus. Gene family variation reflected the expansion and contraction of orthologous genes among Hericium species. Based on genomic bioinformation, we identified the candidate genes associated with the mating system, carbohydrate-active enzymes, and secondary metabolite biosynthesis. Furthermore, metabolite profiling and comparative gene clusters analysis provided strong evidence for the biosynthetic pathway of erinacines in H. rajendrae. This work provides the genome of H. rajendrae for the first time, and enriches the genomic content of the genus Hericium. These findings also facilitate the application of H. rajendrae in complementary drug research and functional food manufacturing, advancing the field of pharmaceutical and functional food production involving H. rajendrae.

ABSTRACT The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.

ABSTRACT Laetiporus sulphureus mushroom is a complementary and alternative medicine that has anticancer, antioxidation, and analgesic effects and immunomodulatory activity; it is used as a treatment for cough and rheumatism and is a functional food that can improve physical fitness. Even though L. sulphureus has garnered considerable biotechnological and pharmacological interest due to its excellent cellulose-degrading ability and diverse biological activities, its biosynthetic potential regarding polysaccharides and secondary metabolites has not been thoroughly examined. In this study, we sequenced and assembled the whole genome of a wild L. sulphureus isolate, NWAFU-1, from the Qinling Mountains in China. Comparative genomes analysis revealed genomic differences between subspecies, and phylogenomic analysis revealed evolutionary divergence as well as genome expansion and contraction of individual Polyporaceae family species. Bioinformatics investigation identified candidate genes associated with mating type, polysaccharide synthesis, carbohydrate-active enzymes, and secondary-metabolite biosynthesis, which included multiple terpenoids, nonribosomal peptides, and polyketides. The locations of biosynthetic core genes were mapped and displayed on chromosomes and contigs. Totals of 143 proteins from 126 coding genes were identified and divided into 14 cytochrome P450 families. Furthermore, the biosynthetic network of tetracyclic triterpenoid active components was postulated by genome mining of related genes combined with the molecular network of metabolites. The genome analysis of L. sulphureus in this study improves the understanding of the biosynthesis of active compounds, which will lay a theoretical foundation for subsequent research on active-compound biosynthesis and promote the application of Laetiporus in the field of drug research and functional-food creation. IMPORTANCE L. sulphureus is a parasitic basidiomycete fungus that causes brown rot. The fruiting bodies of L. sulphureus are used as ancient medicines in China and Europe to cure cancer, analgesia, cough, and rheumatism and are considered a functional food that regulates the body and improves health. L. sulphureus was inferred to be a tetrapolar system based on a high-quality genome, which will aid molecular breeding and artificial farming. Screening polysaccharide synthesis candidate genes and comparing carbohydrate-associated genes in brown-rot basidiomycetes help understand their growth. Identifying core genes for secondary-metabolite biosynthesis, gene cluster family analysis, and comparative cluster analysis will guide heterologous-biosynthesis investigations of these genes and help elucidate the biosynthetic pathways for L. sulphureus bioactive natural components. The biosynthesis network of tetracyclic triterpenes was mapped using metabolite profiling and genome scanning. This work explores the biosynthetic capacity of L. sulphureus-derived natural products and lays the foundation for biosynthetic studies of them.

The culinary medicinal mushroom Hericium erinaceus holds significant global esteem and has garnered heightened interest within increasingly ageing societies due to its pronounced neuroprotective and anti-neuroinflammatory properties. Within this study, two novel diterpenes, 16-carboxy-13-epi-neoverrucosane (1) and Erinacine L (2); three known xylosyl cyathane diterpenoids, Erinacine A (3), Erinacine C (4), and Erinacine F (5); and four lanostane-type triterpenoids, and three cyclic dipeptides (10–12), in addition to orcinol (13), were isolated from the rice-based cultivation medium of H. erinaceus. Their structures were determined by NMR, HR-ESI-MS, ECD, and calculated NMR. Compound 1 marks a pioneering discovery as the first verrucosane diterpene originating from basidiomycetes, amplifying the scope of fungal natural product chemistry, and the intricate stereochemistry of Compound 5 has been comprehensively assessed for the first time. Compounds 2–5 not only showed encouraging neurotrophic activity in rat adrenal pheochromocytoma PC-12 cells, but also significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia cell cultures with IC50 values as low as 5.82 ± 0.18 μM. To elucidate the mechanistic underpinnings of these bioactivities, molecular docking simulation was used to analyze and support the interaction of 1 and 2 with inducible NO synthase (iNOS), respectively. In particular, compound 2, a cyathane-xyloside containing an unconventional hemiacetal moiety, is a compelling candidate for the prevention of neurodegenerative diseases. In summation, this investigation contributes substantively to the panorama of fungal diterpene structural diversity, concurrently furnishing additional empirical substantiation for the role of cyathane diterpenes in the amelioration of neurodegenerative afflictions.

Fusarium species are among the filamentous fungi with the most pronounced impact on agricultural production and human health. The mycotoxins produced by pathogenic Fusarium not only attack various plants including crops, causing various plant diseases that lead to reduced yields and even death, but also penetrate into the food chain of humans and animals to cause food poisoning and consequent health hazards. Although sporadic studies have revealed some of the biosynthetic pathways of Fusarium toxins, they are insufficient to satisfy the need for a comprehensive understanding of Fusarium toxin production. In this study, we focused on 35 serious pathogenic Fusarium species with available genomes and systematically analyzed the ubiquity of the distribution of identified Fusarium- and non-Fusarium-derived fungal toxin biosynthesis gene clusters (BGCs) in these species through the mining of core genes and the comparative analysis of corresponding BGCs. Additionally, novel sesterterpene synthases and PKS_NRPS clusters were discovered and analyzed. This work is the first to systematically analyze the distribution of related mycotoxin biosynthesis in pathogenic Fusarium species. These findings enhance the knowledge of mycotoxin production and provide a theoretical grounding for the prevention of fungal toxin production using biotechnological approaches.

Agaricus bitorquis, an emerging wild mushroom with remarkable biological activities and a distinctive oversized mushroom shape, has gained increasing attention in recent years. Despite its status as an important resource of wild edible fungi, knowledge about this mushroom is still limited. In this study, we used the Illumina NovaSeq and Nanopore PromethION platforms to sequence, de novo assemble, and annotate the whole genome and mitochondrial genome (mitogenome) of the A. bitorquis strain BH01 isolated from Bosten Lake, Xinjiang Province, China. Using the genome-based biological information, we identified candidate genes associated with mating type and carbohydrate-active enzymes in A. bitorquis. Cluster analysis based on P450 of basidiomycetes revealed the types of P450 members of A. bitorquis. Comparative genomic, mitogenomic, and phylogenetic analyses were also performed, revealing interspecific differences and evolutionary features of A. bitorquis and A. bisporus. In addition, the molecular network of metabolites was investigated, highlighting differences in the chemical composition and content of the fruiting bodies of A. bitorquis and A. bisporus. The genome sequencing provides a comprehensive understanding and knowledge of A. bitorquis and the genus Agaricus mushrooms. This work provides valuable insights into the potential for artificial cultivation and molecular breeding of A. bitorquis, which will facilitate the development of A. bitorquis in the field of edible mushrooms and functional food manufacture.

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.

In the original publication, there were publisher errors in the names of authors Zhen-xin Wang, Xi-long Feng and Jin-ming Gao and affiliation (1) of the first, second, fourth and fifth authors (name of the Key Laboratory and city) [...]

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.

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.

Inonotus hispidus mushroom is a popular edible and medicinal mushroom with a long history of use. It is well known as a medicinal fungus with various health benefits for its significant anticancer and immunomodulatory activities. Over the last 60 years, secondary metabolites derived from I. hispidus and their biological activities have been discovered and investigated. Structurally, these compounds are mainly polyphenols and triterpenoids, which have anticancer, anti-inflammatory, antioxidant, antimicrobial, and enzyme inhibitor activities. Here, the secondary metabolites derived from I. hispidus and their activities were systematically and comprehensively classified and summarized, and the biosynthetic pathway of stylylpyrones was deduced and analyzed further. This review contributes to our understanding of I. hispidus and will help with research into natural product chemistry, pharmacology, and the biosynthesis of I. hispidus metabolites. According to this review, I. hispidus could be a promising source of bioactive compounds for health promotion and the development of functional foods.

Hericium mushrooms are a group of rare medicinal mushrooms that have attracted considerable attention worldwide. In order to gain insight into the current trends and frontiers of Hericium research, we conducted a comprehensive search of the Web of Science (WOS) database to identify relevant literature on Hericium research. Following an optimised search strategy and careful removal of duplicate entries, a total of 839 documents were selected from the core WOS database for bibliometric analysis. We used VOSviewer to visualize the co-occurrence network between publishing organizations, while CiteSpace allowed us to visualize and analyse the national co-occurrence network, author co-occurrence network, keyword co-linearity, keyword clustering and co-citation mapping. Our analysis revealed a significant and continuous increase in the number of publications related to Hericium mushrooms, with a peak observed in 2021. Examination of publication statistics by country (region) and institution identified China and Universiti Malaysia as the leading contributors in their respective fields, with active collaboration with other countries and institutions. The analysis of author co-occurrence suggests that inter-author communications and collaborations may be geographically limited by the research institutions to which they belong. Various keyword-based analyses highlighted the structural diversity and bioactivities of small molecule compounds derived from Hericium mushrooms, underscoring their potential health-protective effects as rare food and medicinal mushrooms. Through co-citation analysis, we identified J. Agr. Food Chem. as the most cited journal for Hericium mushroom research results, while Yoko Kawagishi of Shizuoka University (Japan) emerged as the most cited researcher in the field. Overall, our findings suggest that research into the potential anti-neurodegenerative properties of Hericium mushrooms is a promising area of investigation, with a focus on elucidating the underlying mechanisms of action.

Ascamycin (ACM) and dealanylascamycin (DACM) are nucleoside antibiotics elaborated by Streptomyces sp. JCM9888. The later shows broad spectrum inhibition activity to various gram-positive and gram-negative bacteria, eukaryotic Trypanosoma and is also toxic to mice, while ascamycin is active against very limited microorganisms, such as Xanthomonas. Both compounds share an unusual 5'-O-sulfonamide moiety which is attached to an adenosine nucleoside. In this paper, we first report on the 30 kb gene cluster (23 genes, acmA to acmW) involved in the biosynthesis of these two antibiotics and a biosynthetic assembly line was proposed. Of them, six genes (AcmABGKIW) are hypothetical genes involved in 5'-O-sulfonamide formation. Two flavin adenine dinucleotide (FAD)-dependent chlorinase genes acmX and acmY were characterized which are significantly remote from acmA-W and postulated to be required for adenine C2-halogenation. Notably gene disruption of acmE resulted in a mutant which could only produce dealanylascamycin but was blocked in its ability to biosynthesize ascamycin, revealing its key role of conversion of dealanylascamycin to ascamycin.