Evaluation of Cordyceps sinensis Quality in 15 Production Areas Using Metabolomics and the Membership Function Method.

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.

Chemical Structures, Biological Activities, and Biosynthetic Analysis of Secondary Metabolites from Agaricus Mushrooms: A Review.

Agaricus mushrooms are an important genus in the Agaricaceae family, belonging to the order Agaricales of the class Basidiomycota. Among them, Agaricus bisporus is a common mushroom for mass consumption, which is not only nutritious but also possesses significant medicinal properties such as anticancer, antibacterial, antioxidant, and immunomodulatory properties. The rare edible mushroom, Agaricus blazei, contains unique agaricol compounds with significant anticancer activity against liver cancer. Agaricus blazei is believed to expel wind and cold, i.e., the pathogenic factors of wind and cold from the body, and is an important formula in traditional Chinese medicine. Despite its nutritional richness and outstanding medicinal value, Agaricus mushrooms have not been systematically compiled and summarized. Therefore, the present review compiles and classifies 70 natural products extracted from Agaricus mushrooms over the past six decades. These compounds exhibit diverse biological and pharmacological activities, with particular emphasis on antitumor and antioxidant properties. While A. blazei and A. bisporus are the primary producers of these compounds, studies on secondary metabolites from other Agaricus species remain limited. Further research is needed to explore and understand the anticancer and nutritional properties of Agaricus mushrooms. This review contributes to the understanding of the structure, bioactivity, and biosynthetic pathways of Agaricus compounds and provides insights for the development of functional foods using these mushrooms.

Functional Characterization of Sesquiterpene Synthases and P450 Enzymes in Flammulina velutipes for Biosynthesis of Spiro [4.5] Decane Terpene.

Flammulina velutipes, a popular edible mushroom, contains sesquiterpenes with potential health benefits. We characterized 12 sesquiterpene synthases and one P450 enzyme in F. velutipes using Aspergillus oryzae as a heterologous expression system, culminating in the biosynthesis of 16 distinct sesquiterpene compounds. An enzyme encoded by the axeB gene responsible for the synthesis of the spiro [4.5] decane compound axenol was discovered, and the mechanism of spirocycle formation was elucidated through quantum mechanical calculations. Furthermore, we delineated the role of a P450 enzyme colocated with AxeB in producing the novel compound 3-oxo-axenol. Our findings highlight the diverse array of sesquiterpene skeletons and functional groups biosynthesized by these enzymes in F. velutipes and underscore the effectiveness of the A. oryzae system as a heterologous host for expressing genes in the Basidiomycota genome. These insights into the biosynthesis of bioactive compounds in F. velutipes have significant implications for functional food and drug development.

Biochemical characterization of a multiple prenyltransferase from Tolypocladium inflatum.

Prenylation plays a pivotal role in the diversification and biological activities of natural products. This study presents the functional characterization of TolF, a multiple prenyltransferase from Tolypocladium inflatum. The heterologous expression of tolF in Aspergillus oryzae, coupled with feeding the transformed strain with paxilline, resulted in the production of 20- and 22-prenylpaxilline. Additionally, TolF demonstrated the ability to prenylated the reduced form of paxilline, ß-paxitriol. A related prenyltransferase TerF from Chaunopycnis alba, exhibited similar substrate tolerance and regioselectivity. In vitro enzyme assays using purified recombinant enzymes TolF and TerF confirmed their capacity to catalyze prenylation of paxilline, ß-paxitriol, and terpendole I. Based on previous reports, terpendole I should be considered a native substrate. This work not only enhances our understanding of the molecular basis and product diversity of prenylation reactions in indole diterpene biosynthesis, but also provides insights into the potential of fungal indole diterpene prenyltransferase to alter their position specificities for prenylation. This could be applicable for the synthesis of industrially useful compounds, including bioactive compounds, thereby opening up new avenues for the development of novel biosynthetic strategies and pharmaceuticals. KEY POINTS: • The study characterizes TolF as a multiple prenyltransferase from Tolypocladium inflatum. • TerF from Chaunopycnis alba shows similar substrate tolerance and regioselectivity compared to TolF. • The research offers insights into the potential applications of fungal indole diterpene prenyltransferases.

Natural and engineered xylosyl products from microbial source.

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.

The Complete Genomic Sequence of Microbial Transglutaminase Producer, Streptomyces mobaraensis DSM40587.

Actinomycetes are remarkable natural sources of active natural molecules and enzymes of considerable industrial value. Streptomyces mobaraensis is the first microorganism found to produce transglutaminase with broad industrial applications. Although transglutaminase in S. mobaraensis has been well studied over the past three decades, the genome of S. mobaraensis and its secondary metabolic potential were poorly reported. Here, we presented the complete genome of S. mobaraensis DSM40587 obtained from the German Collection of Microorganisms and Cell Cultures GmbH. It contains a linear chromosome of 7,633,041 bp and a circular plasmid of 23,857 bp. The chromosome with an average GC content of 73.49% was predicted to harbour 6683 protein-coding genes, seven rRNA and 69 tRNA genes. Comparative genomic analysis reveals its meaningful genomic characterisation. A comprehensive bioinformatics investigation identifies 35 putative BGCs (biosynthesis gene clusters) involved in synthesising various secondary metabolites. Of these, 13 clusters showed high similarity (> 55%) to known BGCs coding for polyketides, nonribosomal peptides, hopene, RiPP (Ribosomally synthesized and post-translationally modified peptides), and others. Furthermore, these BGCs with over 65% similarity to the known BGCs were analysed in detail. The complete genome of S. mobaraensis DSM40587 reveals its capacity to yield diverse bioactive natural products and provides additional insights into discovering novel secondary metabolites.

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.

Comparative Genomic Analysis and Metabolic Potential Profiling of a Novel Culinary-Medicinal Mushroom, Hericium rajendrae (Basidiomycota).

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.

Molecular properties, structure, neurotrophic and anti-inflammatory activities of cultured secondary metabolites from the cultures of the mushroom Cyathus striatus CBPFE A06.

Two previously undescribed natural cyathane diterpenoids Me-dentifragilin A (1) and Epi-neocyathin O (2), and three known cyathane diterpenoids 3-5, cyathin O, neocyathin P, and cyathin I, were isolated from the rice medium of the Cyathus striatus CBPFE A06. Their structures were established by NMR spectra, and HR-ESI-MS. Compounds 1-5 displayed encouraging neurotrophic activity in PC-12 cells at doses of 5 µM. Meanwhile, 1-5 significantly inhibited LPS-induced NO generation in BV2 cells with the IC50 values ranging from 2.44 ± 0.16 to 4.33 ± 0.32 µM. Western blot analysis showed that 2 and 4 inhibited the expression of genes involved in nitric oxide (NO) production. Molecular docking revealed that five residues of inducible NO synthase (iNOS) are key residues affecting the interaction of 2 and 4 with iNOS. This study enriches the structural diversity of cyathane diterpenes and adds to the evidence that cyathane diterpenes prevent and treat neurodegenerative diseases.

Unprecedented Neoverrucosane and Cyathane Diterpenoids with Anti-Neuroinflammatory Activity from Cultures of the Culinary-Medicinal Mushroom Hericium erinaceus.

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.

Combination of bioaffinity ultrafiltration-UFLC-ESI-Q/TOF-MS/MS, in silico docking and multiple complex networks to explore antitumor mechanism of topoisomerase I inhibitors from Artemisiae Scopariae Herba.

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.

Bioinformatic Analysis of Secondary Metabolite Biosynthetic Potential in Pathogenic Fusarium.

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.

The First Five Mitochondrial Genomes for the Family Nidulariaceae Reveal Novel Gene Rearrangements, Intron Dynamics, and Phylogeny of Agaricales.

The family Nidulariaceae, consisting of five genera including Cyathus, is a unique group of mushrooms commonly referred to as bird's nest fungi due to their striking resemblance to bird's nests. These mushrooms are considered medicinal mushrooms in Chinese medicine and have received attention in recent years for their anti-neurodegenerative properties. However, despite the interest in these mushrooms, very little is known about their mitochondrial genomes (mitogenomes). This study is the first comprehensive investigation of the mitogenomes of five Nidulariaceae species with circular genome structures ranging in size from 114,236 bp to 129,263 bp. Comparative analyses based on gene content, gene length, tRNA, and codon usage indicate convergence within the family Nidulariaceae and heterogeneity within the order Agaricales. Phylogenetic analysis based on a combined mitochondrial conserved protein dataset provides a well-supported phylogenetic tree for the Basidiomycetes, which clearly demonstrates the evolutionary relationships between Nidulariaceae and other members of Agaricales. Furthermore, phylogenetic inferences based on four different gene sets reveal the stability and proximity of evolutionary relationships within Agaricales. These results reveal the uniqueness of the family Nidulariaceae and its similarity to other members of Agaricales; provide valuable insights into the origin, evolution, and genetics of Nidulariaceae species; and enrich the fungal mitogenome resource. This study will help to expand the knowledge and understanding of the mitogenomes in mushrooms.

Iterative-Acting Thioesterase from Polyketide Biosynthesis Accepts Diverse Nucleophilic Alcohols to Yield Oxazole-Containing Esters.

The biosynthesis of antitumor oxazole-containing conglobatin is directed by a multienzyme assembly line of nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS), in which an uncanonical iterative-acting C-terminal thioesterase domain, Cong-TE, ligated two fully elongated chains/conglobatin monomers on the terminal acylcarrier protein and subsequently cyclized the resulting dimer to a C2-symmetric macrodiolide. Screening of the conglobatin producer for secondary metabolites led to the discovery of two new compounds conglactones A (1) and B (2), possessing inhibitory activities to phytopathogenic microorganisms and cancer cells, respectively. The compounds 1 and 2 feature the ester bond-linked hybrid structures consisting of an aromatic polyketide benwamycin I (3) and one (for 1)/two (for 2) molecules of the conglobatin monomer (5). Genetic mutational analysis revealed that the production of 1 and 2 was correlated with the biosynthetic pathways of 3 and 5. Biochemical analysis indicated that 1 and 2 were produced by Cong-TE from 3 and an N-acetylcysteamine thioester form of 5 (7). Furthermore, the substrate compatibility of Cong-TE was demonstrated by enzymatically generating a bunch of ester products from 7 and 43 exotic alcohols. This property of Cong-TE was further validated by producing 36 hybrid esters in the fermentation of conglobatin producer fed with nonindigenous alcohols. This work shows a prospect of developing Cong-TE for green synthesis of valuable oxazole-containing esters, thus complementing the environmentally unfriendly chemosynthesis strategies.

Integrated analysis of topoisomerase I inhibitors from flavonoids of Scutellaria baicalensis Georgi using bioaffinity ultrafiltration UPLC-TripleTOF MS/MS, molecular docking and target-based multiple complex networks.

Scutellaria baicalensis Georgi (SBG) has been widely used as medical plant in East Asia with remarkable anti-cancer activity. However, the underlying mechanisms are still confused. In this study, an integrated analysis was conducted to screen topoisomerase I (topo I) inhibitors from flavonoids of SBG and investigate the anti-cancer mechanisms, containing bioaffinity ultrafiltration UPLC-ESI-TripleTOF-MS/MS, molecular docking, and multiple complex networks. The SBG extract exhibited notable cytotoxic activity on Hela cells. Five flavonoids were identified as potential topo I inhibitors, including skullcapflavone II, wogonin, chrysin, oroxylin A, and tenaxin I. Their ESI-MS/MS spectra showed that RDA reaction and neutral molecule loss were the main fragment patterns. Docking results demonstrated that π-π interaction and the formation of hydrogen bond contributed most to their binding with topo I. The selected compounds, related target proteins and pathways were integrated into target-based multiple complex networks, which consisted of three subnetworks. Statistical and topological analysis of these networks revealed a series of characteristics, including scale-free property with power-law degree distribution, Poisson degree distribution, and small-world property. Chrysin, wogonin, and oroxylin A exhibited as main active components with much higher degree values. Chemical carcinogenesis-receptor activation (hsa05207) was considered as critical pathway due to remarkable centrality indexes. Additionally, potential synergistic effect of wogonin and chrysin was observed on the conversion of supercoiled DNA to relaxed forms. These results improved current understanding of flavonoid-rich plants on the treatment of cancer. Moreover, the multi-disciplinary approach provided a new strategy for the research of natural products from medical plants.

The First Whole Genome Sequencing of Agaricus bitorquis and Its Metabolite Profiling.

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.

Secondary Metabolites of Bird's Nest Fungi: Chemical Structures and Biological Activities.

Bird's nest fungi, a general term for species in the family Nidulariaceae, are named for their fruiting bodies that resemble bird's nests. Two of their members, Cyathus stercoreus (Schw.) de Toni. and Cyathus striatus Will. ex Pers., are known as medicinal fungi in Chinese medicine. Bird's nest fungi produce a variety of secondary metabolites that provide natural materials for screening and developing medicinal compounds. This review presents a systematic summary of the literature on the secondary metabolites of bird's nest fungi up to January 2023, including 185 compounds, mainly cyathane diterpenoids, with prominently characterized antimicrobial and antineurodegenerative activities. Our work aims to advance our understanding of bird's nest fungi and support studies on their natural product chemistry, pharmacology, and biosynthesis of secondary metabolites.

High-efficient production of mushroom polyketide compounds in a platform host Aspergillus oryzae.

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.

Progress in pathogenesis research of Ustilago maydis, and the metabolites involved along with their biosynthesis.

Ustilago maydis is a pathogenic fungus that causes corn smut. Because of its easy cultivation and genetic transformation, U. maydis has become an important model organism for plant-pathogenic basidiomycetes. U. maydis is able to infect maize by producing effectors and secreted proteins as well as surfactant-like metabolites. In addition, the production of melanin and iron carriers is also associated with its pathogenicity. Here, advances in our understanding of the pathogenicity of U. maydis, the metabolites involved in the pathogenic process, and the biosynthesis of these metabolites, are reviewed and discussed. This summary will provide new insights into the pathogenicity of U. maydis and the functions of associated metabolites, as well as new clues for deciphering the biosynthesis of metabolites.

The chemical structures and biological activities of indole diterpenoids.

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.