Fungal Phytotoxin Research Articles

Structure Revision of the Fungal Phytotoxin Cavoxin and of Its Corresponding Chroman-4-one Cavoxone by X-ray Crystallography.

Cavoxin (1) was isolated as the main phytotoxin produced by Phoma cava Schulzer, a toxigenic fungus isolated from Castanea spp. Its structure was determined by 1D NMR and MS in 1985 along with that of the corresponding chroman-4-one cavoxone (2), an artifact formed by acid treatment of 1. Since that time cavoxin was shown to be phytotoxic, antifungal, antifeedant, herbicidal, and antirust with potential application in agriculture and medicine. During a study aimed at improving cavoxin's production by P. cava, single crystals for X-ray diffractometric analysis were obtained. The X-ray crystallography characterization confirmed only in part the structure proposed for cavoxin (1), revealing a different substitution pattern on the aromatic ring, as depicted in the revised structure 3.

The incredible story of ophiobolin A and sphaeropsidin A: two fungal terpenes from wilt-inducing phytotoxins to promising anticancer compounds.

Covering: 2000 to 2023This review presents the exceptional story of ophiobolin A (OphA) and sphaeropsidin A (SphA), a sesterterpene and a diterpene, respectively, which were initially isolated as fungal phytotoxins and subsequently shown to possess other interesting biological activities, including promising anticancer activities. Ophiobolin A is a phytotoxin produced by different fungal pathogens, all belonging to the Bipolaris genus. Initially, it was only known as a very dangerous phytotoxin produced by fungi attacking essential cereals, such as rice and barley. However, extensive and interesting studies were carried out to define its original carbon skeleton, which is characterized by a typical 5 : 8 : 5 ring system and shared with fusicoccins and cotylenins, and its phytotoxic activity on host and non-host plants. The biosynthesis of OphA was also defined by describing the different steps starting from mevalonate and through the rearrangement of the acyclic C-25 precursor lead the toxin is obtained. OphA was also produced as a bioherbicide from Drechslera gigantea and proposed for the biocontrol of the widespread and dangerous weed Digitaria sanguinaria. To date, more than sixty ophiobolins have been isolated from different fungi and their biological activities and structure-activity relationship investigated, which were also described using their hemisynthetic derivatives. In the last two decades, thorough studies have been performed on the potential anticancer activity of OphA and its original mode of action, attracting great interest from scientists. Sphaeropsidin A has a similar story. It was isolated as the main phytotoxin from Diplodia cupressi, the causal agent of Italian cypress canker disease, resulting in the loss of millions of plants in a few years in the Mediterranean basin. The damage to the forest, environment and ornamental heritage are noteworthy and economic losses are also suffered by tree nurseries and the wood industry. Six natural analogues of SphA were isolated and several interesting hemisynthetic derivatives were prepared to study its structure-activity relationship. Surprisingly, sphaeropsidin A showed other interesting biological activities, including antibiotic, antifungal, and antiviral. In the last decade, extensive studies have focused on the anticancer activity and original mode of action of SphA. Furthermore, specific hemisynthetic studies enable the preparation of derivatives of SphA, preserving its chromophore, which showed a noteworthy increase in anticancer activity. It has been demonstrated that ophiobolin A and sphaeropsidin A are promising natural products showing potent activity against some malignant cancers, such as brain glioblastoma and different melanomas.

Discovery of a polyketide carboxylate phytotoxin from a polyketide glycoside hybrid by β-glucosidase mediated ester bond hydrolysis.

Fungal phytotoxins cause significant harm to agricultural production or lead to plant diseases. Discovering new phytotoxins, dissecting their formation mechanism and understanding their action mode are important for controlling the harmful effects of fungal phytopathogens. In this study, a long-term unsolved cluster (polyketide synthase 16, PKS16 cluster) from Fusarium species was thoroughly investigated and a series of new metabolites including both complex α-pyrone-polyketide glycosides and simple polyketide carboxylates were identified from F. proliferatum. The whole pathway reveals an unusual assembly and inactivation process for phytotoxin biosynthesis, with key points as follows: (1) a flavin dependent monooxygenase catalyzes Baeyer-Villiger oxidation on the linear polyketide side chain of α-pyrone-polyketide glycoside 8 to form ester bond compound 1; (2) a β-glucosidase unexpectedly mediates the ester bond hydrolysis of 1 to generate polyketide carboxylate phytotoxin 2; (3) oxidation occurring on the terminal inert carbons of 2 by intracellular oxidase(s) eliminates its phytotoxicity. Our work identifies the chemical basis of the PKS16 cluster in phytotoxicity, shows that polyketide carboxylate is a new structural type of phytotoxin in Fusarium and importantly uncovers a rare ester bond hydrolysis function of β-glucosidase family enzymes.

Investigation of the potential role of fusicoccin, a fungal phytotoxin, in mitigating salt stress in onion roots

Fusicoccin is a diterpene glycoside that plays an important role in the regulation of plant growth and development. Fusicoccin produced by Fusicoccum amydali fungus is known to affect plant growth positively with external applications due to its potential to stimulate the tolerance system of plants under stress conditions. In this study, it was aimed to reduce the negative effects of salt (0.15 M NaCl) stress on the germination and growth of onion (Allium cepa L.) bulbs by external fusicoccin (3 µM) application. For this purpose, the germination percentage, root length, root number, fresh weight, mitotic activity, micronucleus frequency, chromosomal abnormality, antioxidant enzyme activity, osmolyte accumulation, cell membrane damage and root anatomical structure were investigated in the current study. Salt stress caused a statistically significant difference (p < 0.05) in all examined parameters. External application of fusicoccin to onion bulbs germinated under salt stress conditions was found to be promising as a plant growth promoter and mitosis stimulator. In addition, fusicoccin application alleviated the harmful effects of salt stress on the chromosome structure and root anatomical structure and protected the cells from the cytotoxic and genotoxic effects of salt. Moreover, this application contributed to the fight against reactive oxygen species of onion plant and increased salt tolerance by regulating the accumulation of osmolyte substances such as proline and antioxidant enzymes such as superoxide dismutase and catalase, and by minimizing cell membrane damage in root cells. In conclusion, this study showed that exogenous application of 3 µM fusicoccin reduced the damage caused by oxidative stress in onion bulbs and served for healthy germination and growth.

Specialized Metabolites Produced by Phytotopatogen Fungi to Control Weeds and Parasite Plants.

Weeds such as parasite plants are one of the most serious pests that farmers are forced to combat since the development of agriculture using different methods including mechanic and agronomy strategies. These pests have generated significant losses of agrarian and herding production, constituting a serious impediment for agricultural activities in reforestation practices and in important infrastructures. All these serious problems have induced the expansive and massive use of synthetic herbicides, which represents one of the main cause of environmental pollution, as well as serious risks for human and animal health. An alternative environmental friendly control method could be the use of bioherbicides based on suitably bioformulated natural products, of which the main ones are fungal phytotoxins. This review covers the literature from 1980 to the present (2022) and concerns fungal phytotoxins with potential herbicidal activity in order to obtain their efficacy as bioherbicides for practical application in agriculture. Furthermore, some bioherbicides based on microbial toxic metabolites are commercially available, and their application in field, mode of action and future perspectives are also discussed.

Status of Phytotoxins Isolated from Necrotrophic Fungi Causing Diseases on Grain Legumes

Fungal phytotoxins can be defined as secondary metabolites toxic to host plants and are believed to be involved in the symptoms developed of a number of plant diseases by targeting host cellular machineries or interfering with host immune responses. As any crop, legumes can be affected by a number of fungal diseases, causing severe yield losses worldwide. In this review, we report and discuss the isolation, chemical, and biological characterization of fungal phytotoxins produced by the most important necrotrophic fungi involved in legume diseases. Their possible role in plant-pathogen interaction and structure-toxicity relationship studies have also been reported and discussed. Moreover, multidisciplinary studies on other prominent biological activity conducted on reviewed phytotoxins are described. Finally, we explore the challenges in the identification of new fungal metabolites and their possible applications in future experiments.

Ferulic acid is a putative surrender signal to stimulate programmed cell death in grapevines after infection with Neofusicoccum parvum.

An apoplectic breakdown from grapevinetrunk diseases (GTDs) has become a serious challenge to viticulture as a consequence of drought stress. We hypothesize that fungal aggressiveness is controlled by a chemical communication between the host and colonizing fungus. We introduce the new concept of a 'plant surrender signal'accumulating in host plants under stress and facilitating the aggressive behaviour of the strain Neofusicoccum parvum (Bt-67) causing Botryosphaeriaceae-related dieback in grapevines. Using a cell-based experimental system (Vitis cells) and bioactivity-guided fractionation, we identify trans-ferulic acid, a monolignol precursor, as a 'surrender signal'. We show that this signal specifically activates the secretion of the fungal phytotoxin fusicoccin A aglycone. We show further that this phytotoxin, mediated by 14-3-3 proteins, activates programmed cell death in Vitis cells. We arrive at a model showing a chemical communication facilitating fusicoccin A secretion that drives necrotrophic behaviour during Botryosphaeriaceae-Vitis interaction through trans-ferulic acid. We thus hypothesize that channelling the phenylpropanoid pathway from this lignin precursor to the trans-resveratrol phytoalexin could be a target for future therapy.

Structure-activity-relationship study of semi-synthetically modified fusicoccins on their stabilization effect for 14-3-3-phospholigand interactions

The diterpene glucoside fusicoccin-A (FC-A) is a fungal phytotoxin that stabilizes the interaction of plant 14-3-3 protein and plasma membrane H+-ATPase by forming a stable ternary complex. Previous studies demonstrated that structurally modified FC-A derivatives exhibit significant antitumor activities but their synthesis involves an explosive reagent, limiting their utility and opportunities for further structure–activity-relationship studies. In this study, we synthesized a series of FC derivatives by introducing various substituents on the fusicoccan scaffold and on the glucoside moiety, and evaluated their stabilization effects on the binding of 14-3-3 to fluorescently labeled mode-1 and mode-3 phosphopeptides. The results showed that introducing an amino group at the 6′-position of the glucoside moiety improves stabilization. Furthermore, cell-based evaluation demonstrated that 6′-amino benzyl 21b exhibits higher antiproliferative activity than previously developed FC agents.

In Vitro Effects of Fungal Phytotoxins on Cancer Cell Viability: First Insight into Structure Activity Relationship of a Potent Metabolite of Cochliobolus australiensis Radicinin.

Natural compounds have always represented an important source for new drugs. Although fungi represent one such viable source, to date, no fungal metabolite has been marketed as an anticancer drug. Based on our work with phytotoxins as potential chemical scaffolds and our recent findings involving three phytopathogenic fungi, i.e., Cochliobolus australiensis, Kalmusia variispora and Hymenoscyphus fraxineus, herein, we evaluate the in vitro anti-cancer activity of the metabolites of these fungi by MTT assays on three cancer cell models harboring various resistance levels to chemotherapeutic drugs. Radicinin, a phytotoxic dihydropyranopyran-4,5-dione produced by Cochliobolus australiensis, with great potential for the biocontrol of the invasive weed buffelgrass (Cenchrus ciliaris), showed significant anticancer activity in the micromolar range. Furthermore, a SAR study was carried out using radicinin, some natural analogues and hemisynthetic derivatives prepared by synthetic methods developed as part of work aimed at the potential application of these molecules as bioherbicides. This investigation opens new avenues for the design and synthesis of novel radicinin analogues as potential anticancer agents.

Pathogenic potential and phytotoxic effects of Coniolariella gamsii Iran 2506C on Iranian knapweed (Centaurea depressa)

Application of fungal phytotoxins is one of the possible solutions to reduce the use of chemical products in agricultural fields. Phytotoxic compounds isolated from phytopathogenic fungi provide a promising source of environmentally friendly herbicides. This paper focuses on the phytotoxic fungus Coniolariella gamsii Iran 2506C as a fungal pathogen against Iranian knapweed (Centaurea depressa) in the western Iran and investigate its phytotoxic constituents. The fungal pathogen was identified on the basis of morphological characteristics and confirmed by sequencing of the internal transcribed spacer (ITS) region and partial LSU rDNA gene. Pathogenicity tests were conducted on the weed seedlings and C. gamsii Iran 2506C isolate with high disease severity was selected for phytotoxin studies. Phytotoxic activity of the isolate was checked by screening the production of phytotoxins, which interestingly inhibited seed germination and seedling growth of Iranian knapweed as compared to wheat in the bioassays. The active metabolites were extracted from cell-free culture filtrate (CFCF) by ethyl acetate and separated by thin layer chromatography (TLC). The results indicated that two out of four spots had phytotoxicity with Rf values of 0.43 and 0.82 on the weed, whereas wheat was not sensitive in the bioassays. Using Gas Chromatography-Mass spectrometry (GC-MS), 3-Carene and Oleic acid were identified as the main constituents and quantified by a gas chromatographic method with 12.7 ± 0.03 and 2.9 ± 0.01 μg ml−1 respectively. This is the first finding presented on the phytotoxic effects of the active metabolites of C. gamsii Iran 2506C and highlights its herbicidal potential which can be used as a biocontrol agent of C. depressa.

Powerful toxic activity of citrinin, a fungal phytotoxin, and its mode of action in onion cells.

The dose-related effects of citrinin (CTN) on various physiological, cytogenetic, biochemical, and anatomical parameters using Allium cepa L. bulbs as a test material were researched in the present study. The physiological parameters examinated were fresh weight, root length, root number, and germination percentage; the cytogenetic parameters were micronucleus (MN) frequency, chromosome aberration (CA), and mitotic index (MI); the biochemical parameters were catalase (CAT), superoxide dismutase (SOD) activities, malondialdehyde (MDA) level, and free proline contents. And the anatomical changes in root tip cells were investigated by cross-sections. For this aim, onion bulbs were splitted four groups as three applications and one control. The bulbs in the control group were treated with distilled water; the bulbs in the application groups were treated with 1 μM, 5 μM, and 10 μM doses of CTN for 7 days. CTN application caused a decrease in the physiological parameters compared to the control group. This treatment created an increase in the frequency of MN and CA, and a reduce in the MI. In addition, it induced a dose-dependent increase in CAT and SOD activities and MDA and proline contents compared to the control group. Moreover, after CTN application, anatomical changes such as flattened nucleus, cell wall thickening, and cell deformation were identified and it was found that these changes reached their maximum at 10 mg/L dose CTN. Concequently, CTN caused inhibitory effects and the Allium test material was found to be a useful bioindicator for monitoring these effects.

Effect of Adjuvants on Herbicidal Activity and Selectivity of Three Phytotoxins Produced by the Fungus, Stagonospora cirsii.

The use of many fungal phytotoxins as natural herbicides is still limited because they cannot penetrate leaf cuticle without injury and a little is known on their selectivity. In order to assess the herbicidal potential of phytotoxic 10-membered lactones (stagonolide A, stagonolide K, and herbarumin I), the selection of adjuvants, the evaluation of selectivity of the toxins and the efficacy of their formulations were performed. Among four adjuvants tested, Hasten™ (0.1%, v/v) increased phytotoxic activity of all the toxins assayed on non-punctured leaf discs of Sonchus arvensis. When assayed on intact leaf fragments of 18 plants species, 10 species were low to moderately sensitive to stagonolide A, while just five and three species were sensitive to stagonolide K and herbarumin I, respectively. Both leaf damage or addition of Hasten™ (0.1%) to the formulations of the compounds considerably increased or altered the sensitivity of plants to the toxins. Stagonolide A was shown to be non-selective phytotoxin. The selectivity profile of stagonolide K and herbarumin I depended on the leaf wounding or the adjuvant addition. Stagonolide A and herbarumin I formulated in 0.5% Hasten™ showed considerable herbicidal effect on S. arvensis aerial shoots. This study supported the potential of the oil-based adjuvant Hasten™ to increase the herbicidal efficacy of natural phytotoxins.

Probing the 14-3-3 Isoform-Specificity Profile of Protein-Protein Interactions Stabilized by Fusicoccin A.

Fusicoccin A (FC) is a fungal phytotoxin that stabilizes protein–protein interactions (PPIs) between 14-3-3 adapter proteins and their phosphoprotein interaction partners. Recently, FC has emerged as an important chemical probe of human 14-3-3 PPIs involved in cancer and neurobiology. These previous studies have established the structural requirements for FC-induced stabilization of 14-3-3·client phosphoprotein complexes; however, the effect of 14-3-3 isoforms on FC activity remains underexplored. This is a relevant question for the continued development of FC variants because there are seven isoforms of 14-3-3 in humans. Despite their sequence and structural similarities, a growing body of experimental evidence supports both tissue-specific expression of 14-3-3 isoforms and isoform-specific functions in vivo. Herein, we interrogate the isoform-specificity profile of FC in vitro using recombinant 14-3-3 isoforms and a library of fluorescein-labeled hexaphosphopeptides mimicking the C-terminal recognition domains of client proteins that are characterized targets of FC in vivo. Our results reveal modest isoform preferences for individual client phospholigands and demonstrate that FC differentially stabilizes PPIs involving 14-3-3σ. Together, these data support the feasibility of developing FC variants with enhanced isoform selectivity.

Exploitation of Fungal Phytotoxin as Natural Herbicide for Ecofriendly Weed Management: Problems and Prospects

Weeds are major problems in crop production, associated with reduction of crop plant growth, reduce the quality by competing for nutrients and water provided to crops and releasing chemicals that suppress crop growth. Current weed control largely relies on chemical herbicide. The increasing prevalence of both herbicide resistant weeds and bans on chemical herbicide use has created a strong option for development of novel method for weed control. Mycoherbicides include phytopathogenic fungi or fungal compounds or fungal cell free broths or fungal crude broth useful for weed control. The major barriers in the application of fungal spores are returns in investment, which may prohibit the development of highly expensive mycoherbicide, and registration may be impeded if safety and efficacy tests required by the environment protection agencies are too critical, dependency on environment conditions for infection and subsequent development are the major barriers for the application of fungal spores as herbicide. The phytotoxin that inhibit the germination and growth of weed species which are produced and released by fungi or other microbes are receiving increased attention for use as weed controls and as herbicides. Fungal phytotoxins often act as the initiator factor for successful pathogenesis. Several phytotoxins are known to be the determinant factor in pathogenesis. Various phytotoxins viz., tentoxin, AAL-toxin, auscaulitoxin aglycone, hydantocidin, thaxtomin and tabtoxin have the potential for use as herbicides. Fungal phytotoxins are great source for the development of new herbicides and offer ecofriendly alternative approach to weed control. The use of fungal phytotoxins has stimulated the search for alternative to chemical weed control. This review is to highlight the potential of fungal phytotoxin in the weed control, their current progress, problems and potential in their exploitation as Mycoherbicides.

Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A Against Clinical Isolates of Antibiotic-Resistant Bacteria.

Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties.

Auxin action in developing maize coleoptiles: challenges and open questions

ABSTRACT The year 2020 marks the 150th anniversary of the elucidation of the process of plant organ growth at the cellular level by Julius Sachs (1870). In this Addendum to a Review Article in Molecular Plant, we describe this fundamental discovery and argue that the etiolated grass coleoptile still represents the system of choice for the experimental analysis of auxin (indole-3-acetic acid, IAA)-action. With reference to the phenomenon of ‘tissue tension’, we discuss the acid-growth hypotheses of IAA-induced wall loosening and the process of vacuolar expansion, respectively. IAA-mediated elongation appears to be independent of wall acidification, and may be regulated via the secretion of glycoproteins into the outer epidermal wall, whereby turgor (and tissue) pressure provides the ‘driving force’ for growth. As predicted by the “acid growth-hypothesis”, the fungal phytotoxin Fusicoccin (Fc) induces organ elongation via the rapid secretion of protons. We conclude that “cell elongation” can only be understood at the level of the entire organ that displays biomechanical features not established by single cells. This systems-level approach can be traced back to the work of Sachs (1870).

Dirhamnolipid Produced by the Pathogenic Fungus Colletotrichum gloeosporioides BWH-1 and Its Herbicidal Activity.

Fungal phytotoxins used as ecofriendly bioherbicides are becoming efficient alternatives to chemical herbicides for sustainable weed management. Previous study found that cultures of the pathogenic fungus Colletotrichum gloeosporioides BWH-1 showed phytotoxic activity. This study further isolated the major phytotoxin from cultures of the strain BWH-1 using bioactivity-guided isolation, by puncturing its host plant for an activity test and analyzing on the HPLC-DAD-3D mode for a purity check. Then, the active and pure phytotoxin was characterized as a dirhamnolipid (Rha-Rha-C10-C10) using the NMR, ESIMS, IR and UV methods. The herbicidal activity of dirhamnolipid was evaluated by the inhibition rate on the primary root length and the fresh plant weight of nine test plants, and the synergistic effect when combining with commercial herbicides. Dirhamnolipid exhibited broad herbicidal activity against eight weed species with IC50 values ranging from 28.91 to 217.71 mg L−1 and no toxicity on Oryza sativa, and the herbicidal activity could be synergistically improved combining dirhamnolipid with commercial herbicides. Thus, dirhamnolipid that originated from C. gloeosporioides BWH-1 displayed the potential to be used as a bioherbicide alone, or as an adjuvant added into commercial herbicides, leading to a decrease in herbicides concentration and increased control efficiency.

Effect of cultural conditions on the production of radicinin, a specific fungal phytotoxin for buffelgrass (Cenchrus ciliaris) biocontrol, by different Cochlioboulus australiensis strains

Radicinin is a phytotoxic fungal dihydropyranopyran-4,5-dione under evaluation for the development of a target-specific bioherbicide for invasive buffelgrass (Cenchrus ciliaris) control. It has already demonstrated high toxicity on host plants, low toxicity to native plants and no negative effects on zebrafish embryos. To continue these studies at the whole-plant level there is a need to obtain much larger quantities of radicinin, either by optimizing its large-scale production by fungal fermentation or through its total stereoselective synthesis. A rapid and sensitive HPLC method for quantification of radicinin in complex mixtures has been developed in order to evaluate its production by different Cochliobolus australiensis strains and in different cultural conditions. The analysis proved that radicinin is not produced by all the strains tested and its synthesis is strongly affected by cultural conditions. The HPLC method could be useful in selecting the best fungal source for the production of this promising potential bioherbicide.

Phytotoxins produced by pathogenic fungi of agrarian plants

This review, covering the literature from 1965 to present (2018), treats of phytotoxins produced by fungi responsible of heavy diseases of important agrarian crops, including legumes, cereals, fruit trees, vegetables and crops for oil seed production. The symptoms induced on the infected plants are reported and the heavy economical losses caused by the diseases were also described. The chemical characterization and biological activity of the fungal phytotoxins, belonging to the different classes of natural compounds, is reported. In some cases, the probable role played by phytotoxins in the induction of plant disease symptoms is described as well as the results of structure–activity relationship and mode of action studies. The potential application in agriculture and in medicine for some of them is also discussed highlighting the increase in safety and the practical advantages.

Phytotoxins produced by Lasiodiplodia laeliocattleyae involved in Botryosphaeria dieback of grapevines in Brazil.

Botryosphaeria dieback (BD) is an important trunk disease affecting grapevines. Several Lasiodiplodia species have been shown to be involved in BD affecting the perennial organs of grapevine, mainly causing cankers. ( R )-(-)-mellein and tyrosol, two well-known fungal phytotoxins, were isolated from the organic extract of culture filtrate of Lasiodiplodia laeliocattleyae (syn. egyptiacae ), which had been isolated from grapevines affected by BD in Brazil. This increases knowledge of the secondary metabolites produced by Lasiodiplodia species, confirming that ( R )-(-)-mellein is a toxin typically produced by Botryosphaericeae species.