Names | |
---|---|
Other names Muconomycin A | |
Identifiers | |
ECHA InfoCard | 100.164.324 |
Properties | |
C27H34O9 | |
Molar mass | 502.560 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Verrucarin A is a chemical compound that belongs in the class of trichothecenes, a group of sesquiterpene toxins produced by several fungi, namely from the Fusarium species, that are responsible for infecting food grains. It was first described in 1962. [1] Within the skeleton of the basic trichothecene structure, the olefin and epoxide are crucial for toxicity; ester functionalities and hydroxyl groups often contribute to the toxicity, thereby rendering verrucarin A as one of the most lethal examples.[ citation needed ] The mechanism of action for this class of toxins mainly inhibits protein biosynthesis by preventing peptidyl transferase activity. Although initially thought to be potentially useful as anticancer therapeutics, numerous examples of trichothecene derivatives were shown to be too toxic for clinical use.
Verrucarin A is classified as a type D trichothecene based on its substitution pattern in the 12,13-epoxytrichothec-9-ene (EPT) core structure. Type D differs from types A, B and C by containing an additional ring linking the C-4 and C-15 position. Trichothecenes are generally formed via the mevalonate pathway beginning with the precursor farnesyl pyrophosphate (FPP). [2] After cyclization of FPP to form trichodiene, TRI4 encodes a cytochrome P450 enzyme to catalyze a series of oxygenation events. Upon the addition of three oxygens at C-2, C-11 and the C-12,13 epoxide, the intermediate isotrichodiol is formed. Isotrichodiol then isomerizes, yielding the tricothecane EPT core structure. Subsequently, it is proposed that a series of hydroxylations and acylations occur at C-15 and C-4 which then cyclize at these carbons. [3]
In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two organyl groups. They have the general formula R−O−R′, where R and R′ represent organyl groups. Ethers can again be classified into two varieties: if the organyl groups are the same on both sides of the oxygen atom, then it is a simple or symmetrical ether, whereas if they are different, the ethers are called mixed or unsymmetrical ethers. A typical example of the first group is the solvent and anaesthetic diethyl ether, commonly referred to simply as "ether". Ethers are common in organic chemistry and even more prevalent in biochemistry, as they are common linkages in carbohydrates and lignin.
In organic chemistry, an epoxide is a cyclic ether, where the ether forms a three-atom ring: two atoms of carbon and one atom of oxygen. This triangular structure has substantial ring strain, making epoxides highly reactive, more so than other ethers. They are produced on a large scale for many applications. In general, low molecular weight epoxides are colourless and nonpolar, and often volatile.
An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.
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.
Epoxide hydrolases (EHs), also known as epoxide hydratases, are enzymes that metabolize compounds that contain an epoxide residue; they convert this residue to two hydroxyl residues through an epoxide hydrolysis reaction to form diol products. Several enzymes possess EH activity. Microsomal epoxide hydrolase, soluble epoxide hydrolase, and the more recently discovered but not as yet well defined functionally, epoxide hydrolase 3 (EH3) and epoxide hydrolase 4 (EH4) are structurally closely related isozymes. Other enzymes with epoxide hydrolase activity include leukotriene A4 hydrolase, Cholesterol-5,6-oxide hydrolase, MEST (gene) (Peg1/MEST), and Hepoxilin-epoxide hydrolase. The hydrolases are distinguished from each other by their substrate preferences and, directly related to this, their functions.
T-2 mycotoxin is a trichothecene mycotoxin. It is a naturally occurring mold byproduct of Fusarium spp. fungus which is toxic to humans and other animals. The clinical condition it causes is alimentary toxic aleukia and a host of symptoms related to organs as diverse as the skin, airway, and stomach. Ingestion may come from consumption of moldy whole grains. T-2 can be absorbed through human skin. Although no significant systemic effects are expected after dermal contact in normal agricultural or residential environments, local skin effects can not be excluded. Hence, skin contact with T-2 should be limited.
The trichothecenes are a large family of chemically related mycotoxins. They are produced by various species of Fusarium, Myrothecium, Trichoderma/Podostroma, Trichothecium, Cephalosporium, Verticimonosporium, and Stachybotrys. Chemically, trichothecenes are a class of sesquiterpenes.
Sesquiterpenes are a class of terpenes that consist of three isoprene units and often have the molecular formula C15H24. Like monoterpenes, sesquiterpenes may be cyclic or contain rings, including many unique combinations. Biochemical modifications such as oxidation or rearrangement produce the related sesquiterpenoids. A recent study conducted in the Cosmics Leaving Outdoor Droplets large cloud chamber at CERN, has identified sesquiterpenes—gaseous hydrocarbons that are released by plants—as potentially playing a major role in cloud formation in relatively pristine regions of the atmosphere.
Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi, known as mycotoxins. 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.
Pumiliotoxin 251D is a toxic organic compound. It is found in the skin of poison frogs from the genera Dendrobates, Epipedobates, Minyobates, and Phyllobates and toads from the genus Melanophryniscus. Its name comes from the pumiliotoxin family (PTXs) and its molecular mass of 251 daltons. When the toxin enters the bloodstream through cuts in the skin or by ingestion, it can cause hyperactivity, convulsions, cardiac arrest and ultimately death. It is especially toxic to arthropods, even at low concentrations.
Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids and leukotrienes in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eicosanoid production, this third pathway acts as a signaling pathway wherein a set of enzymes metabolize arachidonic acid to a set of products that act as secondary signals to work in activating their parent or nearby cells and thereby orchestrate functional responses. However, none of these three pathways is limited to metabolizing arachidonic acid to eicosanoids. Rather, they also metabolize other polyunsaturated fatty acids to products that are structurally analogous to the eicosanoids but often have different bioactivity profiles. This is particularly true for the CYP epoxygenases which in general act on a broader range of polyunsaturated fatty acids to form a broader range of metabolites than the first and second pathways of eicosanoid production. Furthermore, the latter pathways form metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins; no such receptors have been fully characterized for the epoxide metabolites. Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and these oxygenase enzymes share similarity between humans and other mammalian animal models. The third pathway consists of a large number of metabolite-forming CYP epoxygenases and the human epoxygenases have important differences from those of animal models. Partly because of these differences, it has been difficult to define clear roles for the epoxygenase-epoxide pathways in human physiology and pathology.
Enediynes are organic compounds containing two triple bonds and one double bond.
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.
Tutin is a poisonous plant derivative found in New Zealand tutu plants. It acts as a potent antagonist of the glycine receptor, and has powerful convulsant effects. It is used in scientific research into the glycine receptor. It is sometimes associated with outbreaks of toxic honey poisoning when bees feed on honeydew exudate from the sap-sucking passion vine hopper insect, when the vine hoppers have been feeding on the sap of tutu bushes. Toxic honey is a rare event and is more likely to occur when comb honey is eaten directly from a hive that has been harvesting honeydew from passionvine hoppers feeding on tutu plants.
Carotol was first isolated by scientists Asahina and Tsukamoto in 1925. It is one of the primary components found in carrot seed oil comprising approximately 40% of this essential oil. This sesquiterpene alcohol is thought to be formed in carrot seeds during the vegetation period. Additionally, studies have shown that carotol may be involved in allelopathic interactions expressing activity as an antifungal, herbicidal and insecticidal agent.
Trichothecium roseum is a fungus in the division Ascomycota first reported in 1809. It is characterized by its flat and granular colonies which are initially white and develop to be light pink in color. This fungus reproduces asexually through the formation of conidia with no known sexual state. Trichothecium roseum is distinctive from other species of the genus Trichothecium in its characteristic zigzag patterned chained conidia. It is found in various countries worldwide and can grow in a variety of habitats ranging from leaf litter to fruit crops. Trichothecium roseum produces a wide variety of secondary metabolites including mycotoxins, such as roseotoxins and trichothecenes, which can infect and spoil a variety of fruit crops. It can act as both a secondary and opportunistic pathogen by causing pink rot on various fruits and vegetables and thus has an economical impact on the farming industry. Secondary metabolites of T. roseum, specifically Trichothecinol A, are being investigated as potential anti-metastatic drugs. Several agents including harpin, silicon oxide, and sodium silicate are potential inhibitors of T. roseum growth on fruit crops. Trichothecium roseum is mainly a plant pathogen and has yet to show a significant impact on human health.
Coronaric acid (leukotoxin or leukotoxin A) is a mono-unsaturated, epoxide derivative of the di-saturated fatty acid, linoleic acid (i.e. 9(Z),12(Z) octadecadienoic acid). It is a mixture of the two optically active isomers of 12(Z) 9,10-epoxy-octadecenoic acid. This mixture is also termed 9,10-epoxy-12Z-octadecenoic acid or 9(10)-EpOME and when formed by or studied in mammalians, leukotoxin.
Debromoaplysiatoxin is a toxic agent produced by the blue-green alga Lyngbya majuscula. This alga lives in marine waters and causes seaweed dermatitis. Furthermore, it is a tumor promoter which has an anti-proliferative activity against various cancer cell lines in mice.
Three-finger toxins are a protein superfamily of small toxin proteins found in the venom of snakes. Three-finger toxins are in turn members of a larger superfamily of three-finger protein domains which includes non-toxic proteins that share a similar protein fold. The group is named for its common structure consisting of three beta strand loops connected to a central core containing four conserved disulfide bonds. The 3FP protein domain has no enzymatic activity and is typically between 60-74 amino acid residues long. Despite their conserved structure, three-finger toxin proteins have a wide range of pharmacological effects. Most members of the family are neurotoxins that act on cholinergic intercellular signaling; the alpha-neurotoxin family interacts with muscle nicotinic acetylcholine receptors (nAChRs), the kappa-bungarotoxin family with neuronal nAChRs, and muscarinic toxins with muscarinic acetylcholine receptors (mAChRs).
Nivalenol (NIV) is a mycotoxin of the trichothecene group. In nature it is mainly found in fungi of the Fusarium species. The Fusarium species belongs to the most prevalent mycotoxin producing fungi in the temperate regions of the northern hemisphere, therefore making them a considerable risk for the food crop production industry.