Mycotoxicology

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Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi, known as mycotoxins. [1] In the food industry it is important to adopt measures that keep mycotoxin levels as low as practicable, especially those that are heat-stable. These chemical compounds are the result of secondary metabolism initiated in response to specific developmental or environmental signals. This includes biological stress from the environment, such as lower nutrients or competition for those available. Under this secondary path the fungus produces a wide array of compounds in order to gain some level of advantage, such as incrementing the efficiency of metabolic processes to gain more energy from less food, or attacking other microorganisms and being able to use their remains as a food source.

Contents

Mycotoxins are made by fungi and are toxic to vertebrates and other animal groups in low concentrations. Low-molecular-weight fungal metabolites such as ethanol that are toxic only in high concentrations are not considered mycotoxins. Mushroom poisons are fungal metabolites that can cause disease and death in humans and other animals; they are rather arbitrarily excluded from discussions of mycotoxicology. Molds make mycotoxins; mushrooms and other macroscopic fungi make mushroom poisons. The distinction between a mycotoxin and a mushroom poison is based not only on the size of the producing fungus, but also on human intention. Mycotoxin exposure is almost always accidental. In contrast, with the exception of the victims of a few mycologically accomplished murderers, mushroom poisons are usually ingested by amateur mushroom hunters who have collected, cooked, and eaten what was misidentified as a harmless, edible species. [2]

Mycotoxins are hard to define and are also very difficult to classify. Mycotoxins have diverse chemical structures, biosynthetic origins, myriad biological effects, and produce numerous different fungal species. Classification generally reflects the training of the categorizer and does not adhere to any set system. Mycotoxins are often arranged by physicians depending on what organ they effect. Mycotoxins can be categorized as nephrotoxins, hepatoxins, immunotoxins, neurotoxins, etc. Generic groups created by cell biologist are teratogens, mutagens, allergens, and carcinogens. Organic chemists have attempted to classify them by their chemical structures (e.g., lactones, coumarins); biochemists according to their biosynthetic origins (polyketides, amino acid-derived, etc.); physicians by the illnesses they cause (e.g., St. Anthony's fire, stachybotryotoxicosis), and mycologists by the fungi that produce them (e.g., Aspergillus toxins, Penicillium toxins). None of these classifications is entirely satisfactory. Aflatoxin, for example, is a hepatotoxic, mutagenic, carcinogenic, difuran-containing, polyketide-derived Aspergillus toxin. Zearalenone is a Fusarium metabolite with potent estrogenic activity; hence, in addition to being called (probably erroneously) a mycotoxin, it also has been labeled a phytoestrogen, a mycoestrogen, and a growth promotant. [3]

Types of mycotoxins

Citrinin

Citrinin was first isolated from Penicillium citrinum prior to World War II; [4] subsequently, it was identified in over a dozen species of Penicillium and several species of Aspergillus (e.g., Aspergillus terreus and Aspergillus niveus), including certain strains of Penicillium camemberti (used to produce cheese) and Aspergillus oryzae (used to produce sake, miso, and soy sauce). [5] More recently, citrinin has also been isolated from Monascus ruber and Monascus purpureus, industrial species used to produce red pigments. [6]

Aflatoxins

The aflatoxins were isolated and characterized after the death of more than 100,000 turkey poults (turkey X disease) was traced to the consumption of a mold-contaminated peanut meal. [7] [8] The four major aflatoxins are called B1, B2, G1, and G2 based on their fluorescence under UV light (blue or green) and relative chromatographic mobility during thin-layer chromatography. Aflatoxin B1 is the most potent natural carcinogen known [9] and is usually the major aflatoxin produced by toxigenic strains. It is also the best studied: in a large percentage of the papers published, the term aflatoxin can be construed to mean aflatoxin B1. However, well over a dozen other aflatoxins (e.g., P1. Q1, B2a, and G2a) have been described, especially as mammalian biotransformation products of the major metabolites. [10] The classic book Aflatoxin: Scientific Background, Control, and Implications, published in 1969, is still a valuable resource for reviewing the history, chemistry, toxicology, and agricultural implications of aflatoxin research.

Fumonisins

Fumonisins were first described and characterized in 1988. [11] The most abundantly produced member of the family is fumonisin B1. They are thought to be synthesized by condensation of the amino acid alanine into an acetate-derived precursor. [12] Fumonisins are produced by a number of Fusarium species, notably Fusarium verticillioides (formerly Fusarium moniliforme = Gibberella fujikuroi), Fusarium proliferatum, and Fusarium nygamai, as well as Alternaria alternata f. sp. lycopersici. [13] [14] These fungi are taxonomically challenging, with a complex and rapidly changing nomenclature which has perplexed many nonmycologists (and some mycologists, too). [15] [16] The major species of economic importance is Fusarium verticillioides, which grows as a corn endophyte in both vegetative and reproductive tissues, often without causing disease symptoms in the plant. However, when weather conditions, insect damage, and the appropriate fungal and plant genotype are present, it can cause seedling blight, stalk rot, and ear rot. [17] Fusarium verticillioides is present in virtually all corn samples. [18] Most strains do not produce the toxin, so the presence of the fungus does not necessarily mean that fumonisin is also present. [19] Although it is phytotoxic, fumonisin B1 is not required for plant pathogenesis. [20] [21]

Ochratoxins

Ochratoxin A was discovered as a metabolite of Aspergillus ochraceus in 1965 during a large screen of fungal metabolites that was designed specifically to identify new mycotoxins. [22] Shortly thereafter, it was isolated from a commercial corn sample in the United States [23] and recognized as a potent nephrotoxin. Members of the ochratoxin family have been found as metabolites of many different species of Aspergillus, including Aspergillus alliaceus, Aspergillus auricomus, Aspergillus carbonarius, Aspergillus glaucus, Aspergillus melleus, and Aspergillus niger. [24] [25] [26] Because Aspergillus niger is used widely in the production of enzymes and citric acid for human consumption, it is important to ensure that industrial strains are nonproducers. [27] [28] Although some early reports implicated several Penicillium species, it is now thought that Penicillium verrucosum, a common contaminant of barley, is the only confirmed ochratoxin producer in this genus. [29] [30] Nevertheless, many mycotoxin reviews reiterate erroneous species lists.

Patulin

Patulin is produced by many different molds but was first isolated as an antimicrobial active principle during the 1940s from Penicillium patulum (later called Penicillium urticae, now Penicillium griseofulvum). The same metabolite was also isolated from other species and given the names clavacin, claviformin, expansin, mycoin C, and penicidin. [31] A number of early studies were directed towards harnessing its antibiotic activity. For example, it was tested as both a nose and throat spray for treating the common cold and as an ointment for treating fungal skin infections [32] However, during the 1950s and 1960s, it became apparent that, in addition to its antibacterial, antiviral, and antiprotozoal activity, patulin was toxic to both plants and animals, precluding its clinical use as an antibiotic. During the 1960s, patulin was reclassified as a mycotoxin.

Trichothecenes

The trichothecenes constitute a family of more than sixty sesquiterpenoid metabolites produced by a number of fungal genera, including Fusarium, Myrothecium, Phomopsis, Stachybotrys, Trichoderma, Trichothecium, and others. [33] [34] [35] The term trichothecene is derived from trichothecin, which was one of the first members of the family identified. All trichothecenes contain a common 12,13-epoxytrichothene skeleton and an olefinic bond with various side chain substitutions. They are commonly found as food and feed contaminants, and consumption of these mycotoxins can result in alimentary hemorrhage and vomiting; direct contact causes dermatitis. [36] [37] [38]

Zearalenone

Zearalenone, a secondary metabolite from Fusarium graminearum (teleomorph Gibberella zeae), was given the trivial name zearalenone as a combination of G. zeae, resorcylic acid lactone, -ene (for the presence of the C-1′ to C-2 double bond), and -one, for the C-6′ ketone. [39] Almost simultaneously, a second group isolated, crystallized, and studied the metabolic properties of the same compound and named it F-2. [40] [41] Much of the early literature uses zearalenone and F-2 as synonyms; the family of analogues are known as zearalenones and F-2 toxins, respectively. Perhaps because the original work on these fungal macrolides coincided with the discovery of aflatoxins, chapters on zearalenone have become a regular fixture in monographs on mycotoxins (see, for example, Mirocha and Christensen [42] and Betina [43] ). Nevertheless, the word toxin is almost certainly a misnomer because zearalenone, while biologically potent, is hardly toxic; rather, it sufficiently resembles 17β-estradiol, the principal hormone produced by the human ovary, to allow it to bind to estrogen receptors in mammalian target cells [44] Zearalenone is better classified as a nonsteroidal estrogen or mycoestrogen. Sometimes it is called a phytoestrogen. For the structure-activity relationships of zearalenone and its analogues, see Hurd [45] and Shier. [46]

Related Research Articles

<span class="mw-page-title-main">Mold</span> Wooly, dust-like fungal structure or substance

A mold or mould is one of the structures that certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not all fungi form molds. Some fungi form mushrooms; others grow as single cells and are called microfungi.

<span class="mw-page-title-main">Aflatoxin</span> Group of poisons produced by moulds

Aflatoxins are various poisonous carcinogens and mutagens that are produced by certain molds, particularly Aspergillus species mainly by Aspergillus flavus and Aspergillus parasiticus. According to the USDA, "They are probably the best known and most intensively researched mycotoxins in the world." The fungi grow in soil, decaying vegetation and various staple foodstuffs and commodities such as hay, maize, peanuts, coffee, wheat, millet, sorghum, cassava, rice, chili peppers, cottonseed, tree nuts, sesame seeds, sunflower seeds, and various cereal grains and oil seeds. In short, the relevant fungi grow on almost any crop or food. When such contaminated food is processed or consumed, the aflatoxins enter the general food supply. They have been found in both pet and human foods, as well as in feedstocks for agricultural animals. Animals fed contaminated food can pass aflatoxin transformation products into milk, milk products, and meat. For example, contaminated poultry feed is the suspected source of aflatoxin-contaminated chicken meat and eggs in Pakistan.

A mycotoxin is a toxic secondary metabolite produced by fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops.

Abraham Z. Joffe (1909–2000) was Professor of Mycology and Mycotoxicology at the Hebrew University, Jerusalem.

<span class="mw-page-title-main">Fumonisin B1</span> Chemical compound

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

<span class="mw-page-title-main">Ochratoxin</span> Group of chemical compounds

Ochratoxins are a group of mycotoxins produced by some Aspergillus species and some Penicillium species, especially P. verrucosum. Ochratoxin A is the most prevalent and relevant fungal toxin of this group, while ochratoxins B and C are of lesser importance.

<span class="mw-page-title-main">Trichothecene</span> Large family of chemically related mycotoxins

Trichothecenes constitute a large group of chemically related mycotoxins. They are produced by fungi of the genera Fusarium, Myrothecium, Trichoderma, Podostroma, Trichothecium, Cephalosporium, Verticimonosporium, Stachybotrys and possibly others. Chemically, trichothecenes are a class of sesquiterpenes.

Fermentek Ltd. is a biotechnological company in the Atarot industrial zone of Jerusalem, Israel. It specializes in the research, development and manufacture of biologically active, natural products isolated from microorganisms as well as from other natural sources such as plants and algae.

<span class="mw-page-title-main">Zearalenone</span> Chemical compound

Zearalenone (ZEN), also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some Fusarium and Gibberella species. Specifically, the Gibberella zeae, the fungal species where zearalenone was initially detected, in its asexual/anamorph stage is known as Fusarium graminearum. Several Fusarium species produce toxic substances of considerable concern to livestock and poultry producers, namely deoxynivalenol, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS) and zearalenone. Particularly, ZEN is produced by Fusarium graminearum, Fusarium culmorum, Fusarium cerealis, Fusarium equiseti, Fusarium verticillioides, and Fusarium incarnatum. Zearalenone is the primary toxin that binds to estrogen receptors, causing infertility, abortion or other breeding problems, especially in swine. Often, ZEN is detected together with deoxynivalenol in contaminated samples and its toxicity needs to be considered in combination with the presence of other toxins.

<span class="mw-page-title-main">Citrinin</span> Chemical compound

Citrinin is a mycotoxin which is often found in food. It is a secondary metabolite produced by fungi that contaminates long-stored food and it can cause a variety of toxic effects, including kidney, liver and cell damage. Citrinin is mainly found in stored grains, but sometimes also in fruits and other plant products.

<span class="mw-page-title-main">Fumonisin B2</span> Chemical compound

Fumonisin B2 is a fumonisin mycotoxin produced by the fungi Fusarium verticillioides and Aspergillus niger.

<span class="mw-page-title-main">Fumonisin</span> Group of chemical compounds

The fumonisins are a group of mycotoxins derived from Fusarium and their Liseola section. They have strong structural similarity to sphinganine, the backbone precursor of sphingolipids.

Fusarium incarnatum is a fungal pathogen in the genus Fusarium, family Nectriaceae. It is usually associated with over 40 phylogenetic species in the natural environment to form the Fusarium incarnatum-equiseti species complex (FIESC). This complex is widespread across the globe in subtropical and temperate regions, resulting in many reported cases of crop diseases. It produces various mycotoxins including trichothecenes zearalenone, causing both plant and animal diseases.

Fusarium sporotrichioides is a fungal plant pathogen, one of various Fusarium species responsible for damaging crops, in particular causing a condition known as Fusarium head blight in wheat, consequently being of notable agricultural and economic importance. The species is ecologically widespread, being found across tropical and temperate regions, and is a significant producer of mycotoxins, particularly trichothecenes. Although mainly infecting crops, F. sporotrichioides-derived mycotoxins can have repercussions for human health in the case of the ingestion of infected cereals. One such example includes the outbreak of alimentary toxic aleukia (ATA) in Russia, of which F. sporotrichioides-infected crop was suspected to be the cause. Although current studies on F. sporotrichioides are somewhat limited in comparison to other species in the genus, Fusarium sporotrichioides has found several applications as a model system for experimentation in molecular biology.

<span class="mw-page-title-main">Vomitoxin</span> Fungal toxic chemical in grains

Vomitoxin, also known as deoxynivalenol (DON), is a type B trichothecene, an epoxy-sesquiterpenoid. This mycotoxin occurs predominantly in grains such as wheat, barley, oats, rye, and corn, and less often in rice, sorghum, and triticale. The occurrence of deoxynivalenol is associated primarily with Fusarium graminearum and F. culmorum, both of which are important plant pathogens which cause fusarium head blight in wheat and gibberella or fusarium ear blight in corn. The incidence of fusarium head blight is strongly associated with moisture at the time of flowering (anthesis), and the timing of rainfall, rather than the amount, is the most critical factor. However, increased amount of moisture towards harvest time has been associated with lower amount of vomitoxin in wheat grain due to leaching of toxins. Furthermore, deoxynivalenol contents are significantly affected by the susceptibility of cultivars towards Fusarium species, previous crop, tillage practices, and fungicide use. It occurs abundantly in grains in Norway due to heavy rainfall.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

Mycotoxins are secondary metabolites produced by filamentous fungi, commonly detected as contaminants in agricultural commodities globally. Exposure to these toxins can be very detrimental to both humans and animal, and can lead to mycotoxicosis, which can be a variety of medical conditions. In animals, exposure through feed can disrupt nutrient digestion, absorption, metabolism, and even affect animal physiology. The most common fungi that produce mycotoxins include Fusarium, Aspergillus, and Penicillium.

Aspergillus ochraceus is a mold species in the genus Aspergillus known to produce the toxin ochratoxin A, one of the most abundant food-contaminating mycotoxins, and citrinin. It also produces the dihydroisocoumarin mellein. It is a filamentous fungus in nature and has characteristic biseriate conidiophores. Traditionally a soil fungus, has now began to adapt to varied ecological niches, like agricultural commodities, farmed animal and marine species. In humans and animals the consumption of this fungus produces chronic neurotoxic, immunosuppressive, genotoxic, carcinogenic and teratogenic effects. Its airborne spores are one of the potential causes of asthma in children and lung diseases in humans. The pig and chicken populations in the farms are the most affected by this fungus and its mycotoxins. Certain fungicides like mancozeb, copper oxychloride, and sulfur have inhibitory effects on the growth of this fungus and its mycotoxin producing capacities.

Penicillium nordicum is an anamorph species of fungus in the genus Penicillium which produces ochratoxin A. Penicillium nordicum contaminates protein rich foods and foods with high NaCl-konzentration. It is mostly found on dry-cured meat products and cheese products

<span class="mw-page-title-main">Fumonisin B4</span> Chemical compound

Fumonisin B4 is a fumonisin mycotoxin produced mainly by the fungi Fusarium proliferatum, Fusarium verticillioides. Recently FB4 has been detected in fungi Aspergillus niger and in several Tolypocladium species.

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See also