Introduction

Historically, the genetics of mushrooms have mostly been studied using two model mushrooms, Coprinopsis cinerea and Schizophylum commune (Raper and Miles 1958; Kües and Casselton 1992). These two species have relatively short life cycles, including sexual development and basidiospore formation, which can be completed in the laboratory. Many mutant strains have been isolated and characterized, and various basic properties of mushroom-forming fungi, such as mating type and fruiting body development, have been analyzed (Kamada 2002; Kües and Navarro-González 2015). These two mushrooms still have good potential as model mushrooms and offer opportunities to analyze new aspects of mushroom biology. Practically, popular cultivated mushrooms, such as Lentinus edodes, Agaricus bisporus, P. ostreatus, P. eryngii, Flammulina velutipes, Agaricus marmoreus, Cyclocybe cylindracea, and Auriculalia heimer, have been a target of breeding and a focus of interest in molecular analysis. Medicinal mushrooms, such as Ganoderma lucidum and Cordyceps militaris, have been used to analyze the biosynthetic pathways of terpenoids. However, many of them have slower growth rates, and it takes several weeks or even months to develop a fruiting body, which is essential for segregation analysis and conventional breeding with repeated crosses. Therefore, genetic properties were analyzed and deduced mostly using the conventional model mushrooms C. cinerea and S. commune.

During the last quarter-century, molecular genetic approaches have evolved into powerful tools for identifying, characterizing, and modifying genes with critical roles in a variety of physiological phenomena. These approaches include the use of molecular markers, transformations, gene targeting, RNA interference (RNAi), and genome editing. Using these techniques, it is possible to rapidly clone a gene responsible for a mutation in forward genetics and to demonstrate the function of a gene in reverse genetics using knockout, knockdown, and overexpression. It is possible to breed a new strain with modified regulation of the gene of interest. On the other hand, genome analysis has become very popular and sequence information of many filamentous fungi is available on the internet, mostly brought by the JGI 1000 fungal genome project (Varga et al. 2019; Miyauchi et al. 2020). Information technology using genome databases has made it easier to analyze individual species of cultivated mushrooms directly. It is possible to perform post-genomic analyses in non-cultivated wild mushrooms, including mycorrhiza, using the genome data of other fungi.

However, to utilize the benefits of combining modern molecular genetic tools and genome information technology, it is essential to have a practical and efficient transformation system and adequate genetic tool elements, such as selection markers. In P. ostreatus, these prerequisites have been well-established, and with easy cultivation and a relatively short life cycle, it is possible to carry out effective and rapid analyses using both forward and reverse genetic approaches. In this mini-review, we discuss recent progress in the molecular genetics of this fungus and demonstrate its status as a model mushroom in research topics such as wood degradation, sexual development, and cell wall structure. Future perspectives on cell biology and mushroom materials are also discussed.

Genetic toolbox for P. ostreatus

In P. ostreatus, genetic markers were first characterized to analyze mating-type genes (Larraya et al. 1999a) and a linkage map was reported (Larraya et al. 2000). These were the starting points for molecular genetic research on this fungus, making it one of the best mushrooms equipped with various experimental techniques. The dikaryotic strain, N001, isolated from Navarra, Spain, and its monokaryotic derivatives, PC9 and PC15 (Larraya et al. 1999b), are distributed worldwide and are used as standard strains for molecular genetic analyses of this fungus. The first genome sequence analysis was performed on these strains (Riley et al. 2014) and recently updated using high-quality new-generation sequencing method (Lee et al. 2021).

Genetic transformation system for P. ostreatus

Transformation of P. ostreatus was first reported by Peng et al. (1992). They described development of a transformation system employing a recombinant plasmid harboring a selectable resistance marker to hygromycin B and recovery of rearranged plasmids from the transformants. Furthermore, the same group reported possible extrachromosomal maintenance of unintentionally isolated recombinant plasmids containing a DNA sequence from bacteriophage P1 (Herzog et al. 1995). In 1996, a recombinant drug-resistant marker to bialaphos was developed and successfully used for transformation (Yanai et al. 1996). Despite their prominent achievements as frontier innovators, these transformation techniques are difficult to reproduce and have not become popular in other laboratories, most likely because of their low efficiency and sensitive protoplast yields, depending on the strain and culture conditions.

A practical and stable transformation system for P. ostreatus was first developed when a novel drug-resistance marker of the systemic fungicide carboxin was developed (Honda et al. 2000). A carboxin-resistance marker was constructed to introduce one amino acid change in a gene encoding the iron-sulfur protein (Ip) subunit of mitochondrial succinate dehydrogenase complex II, which is the target site of a widely used agricultural chemical to control corn-smut pathogens. Being a homologous marker gene, the carboxin resistance gene offers self-cloning and reliable expression when introduced into cells. Moreover, it is dominant and background colonies were seldom observed during the screening. This situation has allowed the optimization of transformation protocols in P. ostreatus and the isolation of a ku80 deletant (Salame et al. 2012) from the monokaryon PC9 (Larraya et al. 1999b), which established a high-frequency gene targeting system by homologous recombination in the absence of a non-homologous end joining (NHEJ) DNA repair system. Using the ku80 deletant, Nakazawa et al. (2016) isolated disruptants of pyrG, whose disruption conferred 5-fluorotinic acid (5-FOA) resistance and demonstrated pyrG-complementary transformation. They developed marker recycling methods for multiple gene disruptions using the counter-selection of pyrG and fcy1, disruption of which confers 5-fluorocytocine (5-FC) resistance. Moreover, a drug-resistance marker for nourseothricin has been developed (Matsunaga et al. 2017). These efforts provide a platform for P. ostreatus as one of the most useful agaricomycetes for molecular genetic studies.

Recently, unstable drug-resistant transformants have been reported in Gelatoporia (formerly Ceriporiopsis) subvermispora, depending on the introduction of a recombinant plasmid harboring a hygromycin-resistance marker (Honda et al. 2019). This result strongly suggests transient and possibly extrachromosomal expression of the marker gene. This plasmid lacks the DNA sequence from the P1 phage reported by Herzog et al. (1995). It is plausible that similar transient transformations can occur in many other transformation systems, depending on the balance between screening pressure and the expression level of the selection marker gene. Additionally, the mode of action of the marker gene is important for detecting transient transformation. The hygromycin resistance marker encodes a hygromycin phosphotransferase, which inactivates the drug. It can confer different levels of drug resistance depending on its expression levels, allowing transient drug-resistant transformants to be selected under suitable screening conditions. Using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing system in P. ostreatus, Koshi et al. (2022, also see below) demonstrated that a plasmid expressing Cas9 and guide RNA (gRNA) allows successful genome editing through transient expression of these genes as well as hygromycin resistance markers used for temporal screening of the transformant. In the future, the transient expression of introduced genes could be used for various objectives, such as marker recycling. However, the integration of foreign DNA fragments at random sites on chromosomes can be a potential problem, as in the case of stable transformations.

CRISPR/Cas9 technologies in mushrooms

CRISPR/Cas9 is an adaptive immune system found in archaea and bacteria (Song et al. 2019) that has recently been utilized as a versatile gene-targeting tool. CRISPR/Cas9 is composed of two main parts: a Cas9 endonuclease for generating double-stranded DNA breaks (DSBs) and a single guide RNA (sgRNA) to recruit Cas9 to the target site on the chromosome through the formation of hybrid duplex nucleotides. After targeting DSBs, errors sometimes occur during the NHEJ repair process, introducing mutations at the target site. CRISPR/Cas9-assisted gene targeting protocols are divided into two major strategic categories: DNA-based and pre-assembled Cas9 ribonucleoprotein (RNP)-based methods. The former introduces foreign DNA, such as a recombinant plasmid containing expression cassettes for both Cas9 and sgRNA. The latter introduces the Cas9-sgRNA RNP complex, which was prepared or purchased separately, followed by a pre-assembly step in vitro.

Unlike conventional gene targeting using homologous recombination, CRISPR/Cas9 does not require NHEJ-deficient host strains, such as ku or lig4 deletants, which are isolated only in a limited number of mushroom species, such as S. commune (De Jong et al. 2010), C. cinerea (Nakazawa et al. 2011), and P. ostreatus (Salame et al. 2012). Thus, this method can be applied to other agaricomycetes using a practical genetic transformation system. Recently, the DNA-mediated CRISPR/Cas9 was reported in agaricomycetes, such as C. cinerea (Sugano et al. 2017), G. lingzhi (Qin et al.

Wood degradation

Some agaricomycetes, called “wood-rot fungi,” act as key decomposers in forest ecosystems by degrading the complex lignocellulose matrix. Elucidation of the mechanisms underlying degradation of lignin, a recalcitrant heteropolymer, by these fungi, especially by “white-rot fungus,” would contribute to the development of new methods for efficient and ecofriendly utilization of lignocellulose as a sustainable resource. Lignin degradation mechanisms can also be utilized to remove persistent organic pollutants from the environment (Mori et al. 2021).

Early progress in elucidating wood degradation mechanisms was achieved using the white-rot fungus Phanerochaete chrysosporium. Various enzymes that may play important roles in the degradation of cellulose, hemicellulose, and lignin have been characterized, and the genes encoding these enzymes have been cloned. Following this, a special kind of LME, the versatile peroxidase (VP), was isolated and characterized in P. ostreatus (Kamitsuji et al. 2004) and P. eryngii (Martínez et al. 1996), and recombinant enzymes produced using homologous (Tsukihara et al. 2006) and bacterial expression systems (Fernández-Fueyo et al. 2014) were characterized to demonstrate the structure and functional relationship of these enzymes, respectively. Since genome analysis has become popular in filamentous fungi through the JGI 1000 fungal genome project, an increasing number of wood-rot fungi have been used to analyze wood degradation mechanisms. It is possible to carry out transcriptomic, proteomic, and metabolomic analyses using various fungi, which reveal the common and unique features of these species. Substantial efforts have been devoted to elucidating the mechanisms of wood degradation over the years using various approaches (Fernandez-Fueyo et al. 2012; Zhang et al. 2019; Kijpornyongpan et al. 2022).

However, low accessibility to molecular genetic approaches, especially gene targeting, has prevented the elucidation of which mechanisms and factors are actually required for the biodegradation of natural wood substrates, as it is difficult to examine the precise effects of the loss of each mechanism or factor. P. ostreatus is a unique white-rot fungus for which many useful molecular genetic tools, including efficient gene targeting, are available (Honda et al. 2000; Salame et al. 2012; Nakazawa et al. 2016; Matsunaga et al. 2017), making it a valuable model for studying lignocellulose degradation using a molecular genetics approach. Here, we review recent studies investigating the mechanisms underlying lignin degradation by P. ostreatus.

Genes for degrading enzymes

Nine lignin-modifying peroxidase-encoding genes have been predicted in the genome of P. ostreatus (Knop et al. 2015): three were predicted to be versatile peroxidases (VPs) and six were predicted to be manganese peroxidases (MnPs) (Fernández-Fueyo et al. 2014). These white-rot fungi-specific peroxidases are considered key players in lignin degradation because they can oxidize model lignin compounds and depolymerize synthetic lignin, including the dehydrogenase polymer lignin, in vitro (Kondo et al. 1990; Eggert et al. 1996). However, the natural lignin in plant cell walls is distinct from synthetic molecules; for example, natural lignin is a complex water-insoluble heteropolymer. To demonstrate that these enzymes play an important role in natural lignin degradation, single-gene deletions generated by homologous recombination were analyzed. Salame et al. (2014) showed that vp2 deletion slightly reduces the lignocellulose-degrading ability of cotton stalks, suggesting that VP2 is dispensable for lignin degradation by P. ostreatus, probably because of the redundancy between VPs and MnPs (Salame et al. 2013). Recently, CRISPR/Cas9 has been used to generate multiple gene disruptants of mnp and vp. Additionally, one laccase-encoding gene, lac2, was disrupted because its transcript accumulation was high when grown on beech wood sawdust medium supplemented with wheat bran (BWS; Wu et al. 2020). Lignin-degrading abilities were mostly lost in the vp2/vp3/mnp3/mnp6/mnp2/lac2 sextuple-gene disruptants but not in the vp2/vp3/mnp3/mnp6/mnp2 and vp2/vp3/mnp3/mnp6/lac2 quintuple-gene disruptants grown on BWS, clearly showing their essential role (Nakazawa et al. 2023b). This is the first experimental evidence indicating that these LMEs play essential roles in wood lignin biodegradation by white-rot fungi.

Genes for regulators of lignocellulose degradation

The availability of a reverse genetic approach based on high-frequency gene targeting and a forward genetic approach using genome sequence information have allowed for the identification of various regulators possibly involved in the transcriptional expression of lignocellulose-degrading enzymes in P. ostreatus (Table 2). For example, Wtr1 and Gat1, agaricomycete-specific Zn2Cys6 and GATA DNA-binding transcription factors, respectively, were identified by forward genetic strategies using randomly mutagenized strains (Nakazawa et al. 2017a; 2019). Single gene mutations in wtr1 and gat1, isolated in gene knockout experiments, resulted in defects in the decolorization of the dyes Orange II and Remazol Brilliant Blue R, which are used to examine ligninolytic activity in P. ostreatus on agar plates. They are possible positive regulators of lignin degradation because the lignin-degrading ability in BWS is reduced in single-gene mutants or deletions of these genes. Yoav et al. (2018) analyzed P. ostreatus cre1 deletants and overexpressing strains. Cre1 is a DNA-binding transcription factor homologous to Aspergillus nidulans CreA, which is an important carbon catabolite repressor. Overexpression and deletion of P. ostreatus cre1 resulted in reduced and enhanced lignocellulose-degrading ability of P. ostreatus, respectively (Yoav et al. 2018). In these mutants, the expression levels of many lignocellulose-degrading enzymes (encoding genes) on lignocellulose substrates are greatly altered (Wu et al. 2020, 2021a; Yoav et al. 2018). Alfaro et al. (2020) demonstrated that glucose counteracts the wood-dependent induction of cellulolytic enzymes but not lignin degrading peroxidases. It is of interest whether Cre1 and glucose may contribute to the regulation of these genes. Transcriptional changes have also been observed in single-gene mutants of two putative chromatin remodeler-encoding genes, hir1 and chd1, in P. ostreatus (Nakazawa et al. 2017a, b; Wu et al. 2021b). Based on these findings, we isolated single-gene deletions related to histone modifications. Altered expression patterns were observed for some gene deletions (Okuda et al. 2021, unpublished). Future studies are required to investigate how each regulator alters transcriptional expression, which will provide a methodology for the artificial induction and regulation of ligninolytic, cellulolytic, and hemicellulolytic systems.

Table 2 List of genes possibly involved in transcriptional regulation of putative lignocellulose-degrading enzymes in P. ostreatus that have been identified to date

Expanding molecular genetics analyses in other wood-decaying fungi

Functional analysis of the G. subvermispora gene homologous to P. ostreatus gat1 was conducted (Table 2) using DNA-based CRISPR/Cas9. Similar to P. ostreatus gat1 mutants, lignin-degrading abilities were mostly lost in G. subvermispora gat1 disruptants grown on BWS (Nakazawa et al. 2023a). This suggests that Gat1 is a conserved regulator of the ligninolytic system in white-rot fungi. On the other hand, pex1 gene (peroxisomes) is essential for lignin degradation in P. ostreatus, but not in G. subvermispora (Nakazawa et al. 2017b, 2023a). Comparative genomic, transcriptomic, and secretome studies have proposed theories on the diversity of mechanisms underlying lignin (or lignocellulose) degradation in white-rot fungi (Fernandez-Fueyo et al. 2012; Hori et al. 2014). However, these theories have not yet been experimentally examined. Gene targeting experiments in various white-rot fungi would be useful for this purpose. The accumulation of knowledge from “comparative molecular genetics” will reveal the dynamics of these mechanisms during the evolution of white-rot fungi.

Protein secretion pathway

The production of lignocellulose-degrading enzymes can be regulated or affected at post-transcriptional or translational steps. For examples, changes at the transcription level were not consistent with those in enzyme activities of LMEs in some white-rot fungi, such as Phanerochaete chrysosporium and Trametes versicolor (Sakamoto et al. 2010; Přenosilová et al. 2012). One possible mechanism responsible for such inconsistencies may be protein secretion, protein folding, modification, and trafficking (Fig. 1). Investigating the mechanisms or pathways of protein secretion as well as transcriptional regulation may contribute to the enhancement and modulation of the production level of LMEs (and lignin-degrading abilities) by white-rot fungi. However, protein secretion pathways in white-rot fungi have not yet been well studied. Generally, secretory proteins are transported outside of cells through the endoplasmic reticulum, Golgi apparatus, and secretory vesicles in eukaryotes (Shoji et al. 2008) (Fig. 1). Considering that these organelles have hardly been studied in Agaricomycetes, future studies are needed to confirm whether LMEs are also secreted via similar secretion pathways to investigate the possible regulatory mechanisms and/or bottlenecks in their production. Recently, organelles participating in protein secretion were successfully visualized using recombinant fluorescent proteins in P. ostreatus, suggesting differences in the Golgi apparatus between P. ostreatus and ascomycetes (Kurebayashi et al. 2023). These fluorescence microscopy techniques for P. ostreatus are expected to provide new insights into the cell biology of agaricomycetes.

Fig. 1
figure 1

Proposed secretion pathway of proteins in P. ostreatus. This schematic presentation was drawn based on previous studies in Ascomycetes (Shoji et al. 2008) and our recent study that visualized organelles with recombinant fluorescent proteins in P. ostreatus (Kurebayashi et al. 2023)

Sexual development

As one of the most popular and commercially important edible mushrooms worldwide, breeding of P. ostreatus is important. The accelerated development of powerful methodologies for gene targeting, such as CRISPR/Cas9, has allowed molecular breeding to quickly improve the cultivation and food traits of P. ostreatus (Yamasaki et al. 2022) without laborious and time-consuming crossing steps.

Dikayrosis

Fruiting bodies are generally produced from dikaryotic strains, which are formed when two monokaryotic strains with compatible alleles at both A and B loci are fused (Kamada 2002). Therefore, dikaryosis or dikaryon formation is important in the sexual life cycle and is exclusively observed in basidiomycetes. The underlying mechanisms have been investigated in the model tetrapolar agaricomycetes C. cinerea and S. commune (Kamada 2002; Kües and Navarro-González 2015; Raudaskoski 2015). P. ostreatus is also tetrapolar and is evolutionarily close to these model species (Riley et al. 2014). Moreover, our microscopic observations did not reveal any differences in clamp cell morphogenesis or distribution of nuclei in dikaryotic hyphae between P. ostreatus and the conventional model species (Boontawon et al. 2021c; unpublished). However, recent functional analyses of P. ostreatus genes homologous to C. cinerea pcc1 and clp1 (Murata et al. 1998; Inada et al. 2001) suggested some differences in the A- and B-regulated pathways and/or roles of Pcc1 between C. cinerea and P. ostreatus (Boontawon et al. 2021c): like C. cinerea, monokaryotic pcc1 disruptants formed incomplete fruiting bodies without mating, but unlike C. cinerea, no pseudo-clamp cells were observed in their hyphae. At present, it is difficult to further investigate the mechanisms underlying dikaryosis and conduct functional analyses of pcc1 and clp1 in P. ostreatus because monokaryotic strains in which A- and/or B-regulated pathways are activated are not available, unlike in C. cinerea and S. commune (Koltin 1970; Kües 2015). Future studies are needed to generate such P. ostreatus strains, which will enable us to conduct detailed molecular genetic studies on dikaryosis as well as generate monokaryotic or homokaryotic fruiting strains. These strains will be useful for efficient and rapid molecular breeding.

Fruiting body development

Many genes affecting fruiting initiation and development have been identified in C. cinerea and S. commune (Kamada 2002; Ohm et al. 2011). However, the environmental factors and conditions (i.e., nutrients, temperature, and light) that trigger fruiting in P. ostreatus are different from those of model agaricomycetes. For example, a temperature downshift (to 4–18 °C from 25–30 °C) is essential for P. ostreatus, but not C. cinerea in most cases. Heat shock induces fruiting in S. commune (Ohm et al. 2012). Blue light is required for both fruiting initiation and maturation (stipe elongation, pileus expansion, and meiosis in basidia) in C. cinerea (Kües and Navarro-González 2015; Liu et al. 2022a, 2023a). Furthermore, gene disruption analyses suggested that the physiological functions of Hydph16 in vegetative mycelia differ from those of Vmh2 and Vmh3 in aerial hyphae formation. Disruption of hydph16 did not affect hyphal hydrophobicity; however, defects in the hyphal morphology were observed (unpublished data).

Among all previously sequenced agaricomycetes, the number of hydrophobin genes exceeds 10 (Xu et al. 2021a), and S. commune and P. ostreatus possess 13 and 25 predicted hydrophobin genes, respectively (Table 5). It is noteworthy that, based on the data of 47 species of ascomycetes (Li et al. 2021), the average number of predicted hydrophobin genes was 5.30 and the maximum number was only 13 in these ascomycetes. It remains unclear why there are more hydrophobin genes in basidiomycetes (Rineau et al. 2017), what the functions of each of these genes are, and whether there is functional redundancy. Studies on P. ostreatus hydrophobins revealed that the functions of more than 20 predicted hydrophobin genes were partially redundant but tended to have unique functions at different life stages. Moreover, the Δvmh3 strains showed a marked delay in lignin degradation on BWS, which was the first demonstration of the possible effect of hydrophobins on natural substrate degradation by a basidiomycete (Han et al. 2023b) (Fig. 3). Combined with their amphipathic physicochemical properties, this finding suggests that basidiomycetous hydrophobins may have diverse functions not only in aerial hyphae and fruiting body development, but also in physiological phenomena at the interface between fungi and the outer environment.

Table 5 Number of predicted hydrophobin genes in Agaricomycetes

Other phenomena

The following phenomena in P. ostereatus have been reported to be of interest in understanding the biology of basidiomycetes and agaricomycetes.

Small-secreted proteins (SSPs) are produced by many members of the fungal kingdom and typically contain a signal peptide of less than 300 amino acids (Feldman et al. 2020; Kim et al. 2016b). Despite the abundant production of SSPs (between 40 and 60% of the secretome) in most fungal species, only a few of them have been functionally characterized (Kim et al. 2016b) In P. ostreatus, the SSP family (PoSSP) includes genes ssp1-6, which are representative examples of well-characterized SSPs (Feldman et al. 2020). Homologs of PoSSPs have been found in 22 fungal species, 16 of which belong to the order Agaricales. The ssp1 knockdown strains showed reduced expression of genes encoding extracellular aryl alcohol oxidases (AAOs) and intracellular aryl alcohol dehydrogenases (AADs), and overexpression of ssp1 resulted in elevated expression of genes encoding AAOs and AADs (Feldman et al. 2017). However, the mechanisms underlying the effects of SSP1 on these physiological processes remain unclear (Fig. 3, dashed line). In addition, downregulation of other PoSSP genes through RNAi experiments showed limited lignin degradation on natural substrates but an increase in hemicellulose-degrading capacity (Yarden et al. 2023). Based on these results, the functions of PoSSPs appear to be specialized for the saprotrophic lifestyle of P. ostreatus. Another example of an SSP found in Aspergillus oryzae is the hydrophobic surface-binding protein, HsbA. HsbA functions similarly to the hydrophobin RolA in the degradation of hydrophobic polymers (Feldman et al. 2020). Phylogenetic analysis revealed three hsb homolog genes (hsb1-3) in P. ostreatus. However, a single disruption of any of the hsb genes in P. ostreatus had no effect on the morphological phenotype or lignin degradation (unpublished data). Other examples of SSPs include cerato-platanin, a cysteine-rich SSPs that plays an important role in the interactions between fungi and other organisms (Feldman et al. 2020). Based on RNA sequencing data under substrate degradation conditions (Wu et al. 2021a), seven cerato-platanin-coding genes were retrieved from the genome of P. ostreatus PC9, and one gene showed predominantly high expression. The function of the gene has been investigated through gene knockout, and thus far, no relationship with morphological formation or lignin degradation has been found (unpublished data). Because of the range of roles and high number of conserved SSP-encoding genes, it is difficult to predict SSP functions in basidiomycetes using homology comparisons and gene expression analysis. Continuous investigations through gene deletion and phenotypic analysis will be helpful in improving our knowledge and elucidating the functions of other SSPs.

In recent years, P. ostreatus has been used to study fungal-nematode interactions. Plant parasitic nematodes (PPNs) pose a problem in sustainable agriculture (Al-Ani et al. 2022). Therefore, biological control methods for PPNs are needed to ensure the stable production of agricultural products, and the use of nematophagous fungi is expected to be an effective way to control PPNs. Nematophagous fungi can be divided into four types: (A) nematode-trap**, (B) endoparasitic, (C) nematode-toxin-producing, and (D) egg-parasitic fungi (Jiang et al. 2017). P. ostreatus has been recognized as a nematode toxin-producing fungus, and a nematode toxin was recently identified in this fungus (Lee et al. 2023). In this study, mutants lacking the lollipop-shaped structure (toxocysts) were induced by ultraviolet or ethyl methanesulfonate treatment, and these mutants exhibited no cytotoxic activity against the nematode Caenorhabditis elegana. Gas chromatography-mass spectrometry (GC–MS) analysis of the volatiles in toxocysts and bioactivity assays of an identified volatile revealed that 3-Octanone is the cause of nematocidal activity in P. ostreatus. This study clearly demonstrated how nematode toxin-producing fungi kill nematodes and showed that P. ostreatus is a useful model organism for understanding nematode-fungus interactions.

Lectins exist in a wide range of living organisms including fungi and recognize carbohydrates in a non-catalytic, specific, and reversible manner (Singh et al. 2020). In fungi, mushrooms are a rich source of lectin (Singh et al. 2020). Several lectins from mushrooms have been reported to have antiviral, antimicrobial, and immunomodulatory activity (Singh et al. 2020). In the genome of P. ostreatus PC9 strain, a total of 24 genes encoding lectins were predicted (Liu et al. 2023). A lectin named POL (Pleurotus ostreatus Lectin) was identified from fruiting bodies by multiple independent groups (Perduca et al. 2020). It was reported that POL has medical properties such as food-intake suppression and antitumoral activity (Perduca et al. 2020). The immunogenic activity of POL was also reported in hepatitis B virus vaccine therapy (Gao et al. 2013). In recent protein-structure analysis, POL exhibits a novel fold made up of two homologous β-jellyroll domains which each possess a calcium-dependent carbohydrate-binding site (Perduca et al. 2020). Although the structure and medical proprieties of POL have been analyzed, its physiological role in P. ostreatus is still unknown. On the other hand, functions of a galectin-like lectin named Polec2 has been reported recently (Liu et al. 2023). Gene expression of polec2 was induced in response to attack by the storage mite Tyrophagus putrescentiae (Li et al. 2022). The polec2 overexpression strains show higher resistance against T. putrescentiae attack than the wild type. This could be due to induction of more reactive oxygen species, activation of genes involved in mitogen-activated protein kinase (MAPK) pathways, or changes to jasmone and salicylic acid production (Liu et al. 2023). As physiological functions of many lectins in mushrooms are still unknown, results of the Polec2 study highlight the usefulness of molecular genetics of P. ostreatus in understandings functions of mushroom lectins.

Conclusions

With the recent progress in molecular genetic approaches, including post-genomics and genome editing, P. ostreatus provides a good experimental platform for investigating the molecular mechanisms underlying various physiological phenomena in mushrooms. Genome analysis has revealed that many agaricomycetes have redundant genes for substrate degradation, complex and multilayered signal transduction systems, and many genes encoding proteins with unknown functions. Comparative transcriptomics have demonstrated that the expression of many genes is altered under various conditions. It is sometimes difficult to understand the core mechanisms that lead to fundamental changes in cells and side effects. Along with forward genetic analysis, the knockout of multiple genes may help elucidate the molecular mechanisms underlying these complex phenomena. By comparing with other mushrooms, common principal mechanisms among many mushrooms as well as species-specific unique mechanisms will be uncovered using P. ostreatus as a model.