Volatile Organic Compound Profile Fingerprints Using DART–MS Shows Species-Specific Patterns in Fusarium Mycotoxin Producing Fungi

Fungal volatile organic compounds (VOCs) are low-molecular weight fungal metabolites that have high vapor pressure at ambient temperatures and can function as airborne signals. Here, we report a VOC study of several different species of Fusarium. Direct analysis in real time mass spectrometry (DART–MS) was applied for non-invasive VOC fingerprinting of Fusarium isolates growing under standardized conditions. A large number of ions were detected from the headspaces of the Fusarium species sampled here. Ions were detected with distinctively high concentrations in some species. While there were few VOCs produced by only one species, the relative concentrations of VOCs differed between species. The methodology has potential for convenient detection and identification of Fusarium contamination in agricultural commodities.

Multi-mycotoxins and Fungal Contaminants of Wheat from Anambra State, Nigeria

This study was carried out to determine the fungal and mycotoxins contamination of 36 Wheat (Triticum aestivium) samples purchased randomly from the seller of the agricultural produce in local markets of Anambra State, Nigeria. Results from the studies showed that two hundred and three fungal isolates consisting of 18 species of moulds and 5 species of yeasts contaminated the wheat samples at varying degrees. For moulds, Aspergillus species contaminated the samples mostly with (28) isolates followed by Penicillum species (19) isolates while Verticillium species and Cladosporium species had equal least contaminations with (3) isolates each. Among the yeast species, Candida rugosahad the highest number of contamination with (37) isolates followed by Cryptococcus laurentii (31) isolates while Candida stellatoides (9) isolates had the least contamination. Twenty-four fungal metabolites were also recovered. The concentration of trichothecene mycotoxin Deoxynivalenol (2067µg/kg), a protein synthesis and cell proliferation inhibitor in animals exceeded the maximum acceptable limits for human consumption. It can be deduced therefore that wheat circulating in Anambra State, Nigeria are variously contaminated with different xerophilic moulds and mycotoxins which can exert adverse health problems to consumers. Keyword: Wheat samples, fungal contaminants, multi-mycotoxins and market zones

Aflatoxin and Disruption of Energy Metabolism

Aflatoxins constitute a cluster of mycotoxins that are derived from fungal metabolites and are produced from diverse fungi species, especially Aspergillus. They are a collection of closely linked heterocyclic compounds produced predominantly by two filamentous fungi, Aspergillus flavus and Aspergillus parasiticus. They are also known to cause severe health threats to humans and animals, thereby resulting to several complications like immunotoxicity, teratogenicity hepatotoxicity. Aflatoxins interfere with normal metabolic processes. This interference encompasses the regulatory processes that occur throughout the progression of energy metabolism. Thus, the effects of aflatoxins are seen in the inhibition of ATP generation, carbohydrate and lipid metabolism, mitochondrial structure and proteins synthesis. This chapter will focus on the mechanisms of aflatoxin-induced disruption of lipids, carbohydrates, and proteins metabolism, and how they affect the bioenergetic systems.

Effects of Prenatal Exposure to Aflatoxin B1: A Review

Aflatoxins are mycotoxins produced as secondary fungal metabolites. Among them, aflatoxin B1 (AFB1) stands out due to its genotoxic and mutagenic potential, being a potent initiator of carcinogenesis. In this review, the outcomes from the published literature in the past 10 years on the effects of AFB1 pathophysiological mechanisms on embryological and fetal development are discussed. In several animal species, including humans, AFB1 has a teratogenic effect, resulting in bone malformations, visceral anomalies, lesions in several organs, and behavioral and reproductive changes, in addition to low birth weight. The mutagenic capacity of AFB1 in prenatal life is greater than in adults, indicating that when exposure occurs in the womb, the risk of the development of neoplasms is higher. Studies conducted in humans indicate that the exposure to this mycotoxin during pregnancy is associated with low birth weight, decreased head circumference, and DNA hypermethylation. However, as the actual impacts on humans are still unclear, the importance of this issue cannot be overemphasized and studies on the matter are essential.

Natural Dibenzo-α-Pyrones: Friends or Foes?

Natural dibenzo-α-pyrones (DAPs) can be viewed from two opposite angles. From one angle, the gastrointestinal metabolites urolithins are regarded as beneficial, while from the other, the emerging mycotoxin alternariol and related fungal metabolites are evaluated critically with regards to potential hazardous effects. Thus, the important question is: can the structural characteristics of DAP subgroups be held responsible for distinct bioactivity patterns? If not, certain toxicological and/or pharmacological aspects of natural DAPs might yet await elucidation. Thus, this review focuses on comparing published data on the two groups of natural DAPs regarding both adverse and beneficial effects on human health. Literature on genotoxic, estrogenic, endocrine-disruptive effects, as well as on the induction of the cellular anti-oxidative defense system, anti-inflammatory properties, the inhibition of kinases, the activation of mitophagy and the induction of autophagy, is gathered and critically reviewed. Indeed, comparing published data suggests similar bioactivity profiles of alternariol and urolithin A. Thus, the current stratification into hazardous Alternaria toxins and healthy urolithins seems debatable. An extrapolation of bioactivities to the other DAP sub-class could serve as a promising base for further research. Conclusively, urolithins should be further evaluated toward high-dose toxicity, while alternariol derivatives could be promising chemicals for the development of therapeutics.

Discovery of mosquitocides from fungal extracts through a high-throughput cytotoxicity-screening approach

Background Mosquitoes transmit a variety of diseases. Due to widespread insecticide resistance, new effective pesticides are urgently needed. Entomopathogenic fungi are widely utilized to control pest insects in agriculture. We hypothesized that certain fungal metabolites may be effective insecticides against mosquitoes. Methods A high-throughput cytotoxicity-based screening approach was developed to search for insecticidal compounds in our newly established global fungal extract library. We first determined cell survival rates after adding various fungal extracts. Candidate insecticides were further analyzed using traditional larval and adult survival bioassays. Results Twelve ethyl acetate extracts from a total of 192 fungal extracts displayed > 85% inhibition of cabbage looper ovary cell proliferation. Ten of these 12 candidates were confirmed to be toxic to Anopheles gambiae Sua5B cell line, and six showed > 85% inhibition of Anopheles mosquito cell growth. Further bioassays determined a LC50, the lethal concentration that kills 50% of larval or adult mosquitoes, of 122 µg/mL and 1.7 µg/mosquito, respectively, after 24 h for extract 76F6 from Penicillium toxicarium. Conclusions We established a high-throughput MTT-based cytotoxicity screening approach for the discovery of new mosquitocides from fungal extracts. We discovered a candidate extract from P. toxicarium that exhibited high toxicity to mosquito larvae and adults, and thus were able to demonstrate the value of our recently developed approach. The active fungal extracts discovered here are ideal candidates for further development as mosquitocides. Graphical abstract

Toward the Synthesis of the Fungal Metabolite (-)-TAN-2483B

<p>In the search of chemical species with potential therapeutic biological activity, synthetic chemists have looked to nature for inspiration. Molecules built by biological machinery often have structures predisposed for biological interaction. (-)-TAN-2483B and the related compounds (-)-TAN-2483A, and waol A are fungal metabolites that display biological activity in kinase inhibition and parathyroid-induced bone resorption. Though total syntheses of (-)-TAN-2483A and waol A have been achieved, the established methodology does not afford access to (-)-TAN-2483B owing to the unique relative configuration about the ring system. Derivatives of D-galactal have been synthesised, and functionalised at the C-1 and C-2 positions, laying the groundwork for a route to (-)-TAN-2483B and analogues. Using D-galactal derivatives is advantageous as it circumvents some difficult transformations in the existing method for analogue synthesis. The functionalities installed were halide and formyl groups at the C-2 position, and acetylenes at the C-1 position. The synthesis of 2-haloglycals from tri-O-acetyl-D-galactal using N-halosuccinimides was achieved in 32% and <37% for the bromo- and iodo- variants respectively. Vilsmeier-Haack formylation was explored using per-benzylated and per-acetylated galactals as substrates. Formylation of the per-benzylated species was achieved in 78% yield in accordance with literature values. Vilsmeier-Haack formylation on the per-acetylated galactal has not been reported and the glycal was found to be a poor substrate for the formylation. Theories regarding the incompatibility of the per-acetylated species with Vilsmeier-Haack conditions were developed. Ferrier-type alkynylation of the 2-halo/formylglycals was explored, with yields up to 17% and 13% for the bromo- and iodo- species (unoptimised), and 7% for 2-formylglycal (after optimisation studies). The resulting 1-ethynyl-2-formyl/halo-2,3-unsaturated pyrans could be potential intermediates en route to the furanone ring of the target compound.</p>

Toward the Synthesis of the Fungal Metabolite (-)-TAN-2483B

<p>In the search of chemical species with potential therapeutic biological activity, synthetic chemists have looked to nature for inspiration. Molecules built by biological machinery often have structures predisposed for biological interaction. (-)-TAN-2483B and the related compounds (-)-TAN-2483A, and waol A are fungal metabolites that display biological activity in kinase inhibition and parathyroid-induced bone resorption. Though total syntheses of (-)-TAN-2483A and waol A have been achieved, the established methodology does not afford access to (-)-TAN-2483B owing to the unique relative configuration about the ring system. Derivatives of D-galactal have been synthesised, and functionalised at the C-1 and C-2 positions, laying the groundwork for a route to (-)-TAN-2483B and analogues. Using D-galactal derivatives is advantageous as it circumvents some difficult transformations in the existing method for analogue synthesis. The functionalities installed were halide and formyl groups at the C-2 position, and acetylenes at the C-1 position. The synthesis of 2-haloglycals from tri-O-acetyl-D-galactal using N-halosuccinimides was achieved in 32% and <37% for the bromo- and iodo- variants respectively. Vilsmeier-Haack formylation was explored using per-benzylated and per-acetylated galactals as substrates. Formylation of the per-benzylated species was achieved in 78% yield in accordance with literature values. Vilsmeier-Haack formylation on the per-acetylated galactal has not been reported and the glycal was found to be a poor substrate for the formylation. Theories regarding the incompatibility of the per-acetylated species with Vilsmeier-Haack conditions were developed. Ferrier-type alkynylation of the 2-halo/formylglycals was explored, with yields up to 17% and 13% for the bromo- and iodo- species (unoptimised), and 7% for 2-formylglycal (after optimisation studies). The resulting 1-ethynyl-2-formyl/halo-2,3-unsaturated pyrans could be potential intermediates en route to the furanone ring of the target compound.</p>

The Endophytic Fungus Cyanodermella asteris Influences Growth of the Non-Natural Host Plant Arabidopsis thaliana

Cyanodermella asteris is a fungal endophyte from Aster tataricus, a perennial plant from the Northern part of Asia. Here, we demonstrated an interaction of C. asteris with Arabidospis thaliana, Chinese cabbage, rapeseed, tomato, maize or sunflower resulting in different phenotypes such as shorter main roots, massive lateral root growth, higher leaf and root biomass, and increased anthocyanin levels. In a variety of co-cultivation assays, it was shown that these altered phenotypes are caused by fungal CO2, volatile organic compounds, and soluble compounds, notably astins. Astins A, C and G induced plant growth when they were individually included in the medium. In return, A. thaliana stimulates the fungal astin C production during co-cultivation. Taken together, our results indicate a bilateral interaction between the fungus and the plant. A stress response in plants is induced by fungal metabolites while plant stress hormones induced astin C production of the fungus. Interestingly, our results not only show unidirectional influence of the fungus on the plant, but vice versa. The plant is able to influence growth and secondary metabolite production in the endophyte, even when both organisms do not live in close contact, suggesting the involvement of volatile compounds.