Verrucarin A

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Verrucarin A
Verrucarin A structure.png
Names
Other names
Muconomycin A
Identifiers
ECHA InfoCard 100.164.324 OOjs UI icon edit-ltr-progressive.svg
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.

Biosynthesis

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]

Biosynthesis of Verrucarin A.png

Related Research Articles

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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.

<span class="mw-page-title-main">Epoxide</span> Organic compounds with a carbon-carbon-oxygen ring

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.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

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.

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

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<span class="mw-page-title-main">Enediyne</span> Any organic compound containing one double and two triple bonds

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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.

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<span class="mw-page-title-main">Three-finger toxin</span> Toxin protein

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<span class="mw-page-title-main">Nivalenol</span> Type of mycotoxin

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References

  1. Harri, E.; Loeffler, W.; Sigg, H.P.; Stahelin, H.; Tamm, Ch. Stoll Ch.; Wiesinger, D. (1962). "Über die Verrucarine und Roridine, eine Gruppe von cytostatisch hochwirksamen Antibiotica aus Myrothecium-Arten". Helvetica Chimica Acta. 45 (3): 839–853. doi:10.1002/hlca.19620450314.
  2. Dewick, Paul. Medical Natural Products: A Biosynthetic Approach, 3rd edition. John Wiley & Sons Ltd. pp. 187–310. ISBN   9780470742761.
  3. McCormick, Susan; Stanley, April; Stover, Nicholas; Alexander, Nancy (2011). "Trichothecenes: From Simple to Complex Mycotoxins". Toxins. 3 (7): 802–814. doi: 10.3390/toxins3070802 . PMC   3202860 . PMID   22069741.