Cyclochlorotine

Last updated
Cyclochlorotine
Cyclochlorotine.png
Cyclochlorotine 3D ball.png
Names
IUPAC name
1,2-Dichloro-15-ethyl-5,12-bis-hydroxymethyl-9-phenyl-dodecahydro-3a,6,10,13,16-pentaaza-cyclopentac yclohexadecene-4,7,11,14,17-pentaone
Other names
Cyclo[(R)-3-phenyl-β-alanyl-L-seryl-(2α,3α,4α)-3,4-dichloro-L-prolyl-L-2-aminobutanoyl-L-seryl]; Yellowed rice toxin
Identifiers
3D model (JSmol)
ChemSpider
KEGG
PubChem CID
UNII
  • InChI=1S/C24H31Cl2N5O7/c1-2-14-21(35)30-16(10-32)22(36)29-15(12-6-4-3-5-7-12)8-18(34)27-17(11-33)24(38)31-9-13(25)19(26)20(31)23(37)28-14/h3-7,13-17,19-20,32-33H,2,8-11H2,1H3,(H,27,34)(H,28,37)(H,29,36)(H,30,35)/t13-,14+,15-,16+,17+,19-,20+/m1/s1 X mark.svgN
    Key: PMBVHCCVEPYDSN-BADCMNFISA-N X mark.svgN
  • InChI=1/C24H31Cl2N5O7/c1-2-14-21(35)30-16(10-32)22(36)29-15(12-6-4-3-5-7-12)8-18(34)27-17(11-33)24(38)31-9-13(25)19(26)20(31)23(37)28-14/h3-7,13-17,19-20,32-33H,2,8-11H2,1H3,(H,27,34)(H,28,37)(H,29,36)(H,30,35)/t13-,14+,15-,16+,17+,19-,20+/m1/s1
    Key: PMBVHCCVEPYDSN-BADCMNFIBI
  • O=C([C@H](CO)NC1=O)N[C@@H](C2=CC=CC=C2)CC(N[C@H](C(N3[C@H](C(N[C@H]1CC)=O)[C@H](Cl)[C@H](Cl)C3)=O)CO)=O
Properties
C24H31Cl2N5O7
Molar mass 572.44 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Cyclochlorotine [1] (CC), also known as islanditoxin, [2] is a mycotoxin produced by the fungus Penicillium islandicum [3] that causes liver damage and has carcinogenic properties. [4] Japanese researchers confirmed that it was one of three strains of Penicillin fungi responsible for yellowed rice. [2] It is listed as an IARC Group 3 carcinogen.

Chemically, it is a dichlorinated cyclic peptide. [5] Structurally, the only thing that differentiates cyclochlorotine from the plant-derived astins of Aster tataricus , is replacement of a serine with a second 2-aminobutyrate. [6]

Cyclochlorotine is one of the toxins usually found in foods in grains such as rice, wheat, soybeans, peanuts, beans, bread, flour, etc. Such foods serve as medium for the growth of molds such as Penicillium islandicum which in turn release toxins such as cyclochlorotine. [7] Research shows that that biosynthesis of cyclochlorotine is a multi-step mechanism and makes use of a vital component in the last step known as NRPS (CctN). [6]

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.

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.

<span class="mw-page-title-main">Polymyxin</span> Group of antibiotics

Polymyxins are antibiotics. Polymyxins B and E are used in the treatment of Gram-negative bacterial infections. They work mostly by breaking up the bacterial cell membrane. They are part of a broader class of molecules called nonribosomal peptides.

<i>Penicillium roqueforti</i> Species of fungus

Penicillium roqueforti is a common saprotrophic fungus in the genus Penicillium. Widespread in nature, it can be isolated from soil, decaying organic matter, and plants.

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

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.

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.

<i>Penicillium expansum</i> Species of fungus

Penicillium expansum is a psychrophilic blue mold that is common throughout the world in soil. It causes Blue Mold of apples, one of the most prevalent and economically damaging post-harvest diseases of apples.

<span class="mw-page-title-main">Fungus</span> Biological kingdom, separate from plants and animals

A fungus is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the traditional eukaryotic kingdoms, along with Animalia, Plantae and either Protista or Protozoa and Chromista.

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.

Penicillium islandicum is an anamorph species of the genus of Penicillium which produces luteoskyrin, simatoxin, cyclochlorotine, rugulosin, islanditoxin and chitosanase.

Yellowed rice refers to three kinds of rice grains contaminated with different strains of Penicillium fungi—Yellow rice, Citrinum yellow rice, and Islandia yellow rice. These rice grains were first identified in Japan in 1964, after the research was interrupted by World War II. The first of the yellowed rice strains has been linked to shoshin-kakke. Citrinum yellow rice and Islandia yellow rice are not known to have caused any adverse effects in human populations.

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

Penicillium rugulosum is an anamorph species of fungus in the genus Penicillium which produces inulinase, luteoskyrin and (+) rugulosin.

Penicillium viridicatum is a psychrophilic species of fungus in the genus, penicillic acid and citrinin. Penicillium viridicatum can spoil grapes and melons.

Penicillium verrucosum is a psychrophilic fungus which was discovered in Belgium and introduced by Dierckx in 1901. Six varieties of this species have been recognized based primarily on differences in colony colour: P. verrucosum var. album, P. verrucosum var. corymbiferum, P. verrucosum var. cyclopium, P. verrucosum var. ochraceum, P. verrucosum var. melanochlorum and P. verrucosum var. verrucosum. This fungus has important implications in food, specifically for grains and other cereal crops on which it grows. Its growth is carefully regulated in order to reduce food spoilage by this fungi and its toxic products. The genome of P. verrucosum has been sequenced and the gene clusters for the biosyntheses of its mycotoxins have been identified.

Penicillium commune is an indoor fungus belonging to the genus Penicillium. It is known as one of the most common fungi spoilage moulds on cheese. It also grows on and spoils other foods such as meat products and fat-containing products like nuts and margarine. Cyclopiazonic acid and regulovasine A and B are the most important mycotoxins produced by P. commune. The fungus is the only known species to be able to produce both penitrem A and roquefortine. Although this species does not produce penicillin, it has shown to have anti-pathogenic activity. There are no known plant, animal or human diseases caused by P. commune.

Xeromyces is a monotypic genus of fungus in the family Monascaceae. Its only species, Xeromyces bisporus, was first described by L.R. Fraser in 1954. No subspecies are listed in the Catalogue of Life.

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

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.

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

Penicillin Roquefort toxin is a mycotoxin produced by the fungi Penicillium roqueforti. In 1973, PR toxin was first partially characterized by isolating moldy corn on which the fungi had grown. Although its lethal dose was determined shortly after the isolation of the chemical, details of its toxic effects were not fully clarified until 1982 in a study with mice, rats, anesthetized cats and preparations of isolated rat auricles.

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

Luteoskyrin is a carcinogenic mycotoxin with the molecular formula C30H22O12 which is produced by the mold Penicillium islandicum. Luteoskyrin has strong cytotoxic effects. Luteoskyrin can cause the yellow rice disease.

References

  1. Zhou, ZH; Komiyama, M; Terao, K; Shimada, Y (1994). "Effects of cyclochlorotine on myofibrils in cardiomyocytes and on actin filament bundles in fibroblasts in vitro". Nat. Toxins. 2 (6): 378–85. doi:10.1002/nt.2620020607. PMID   7704452.
  2. 1 2 Kushiro, Masayo (2015). "Historical review of researches on yellow rice and mycotoxigenic fungi adherent to rice in Japan". JSM Mycotoxins. 65: 12–23. doi: 10.2520/myco.65.19 .
  3. "Toxicology of Penicillium islandicum". Nature. 191 (4791): 864–865. 1961. Bibcode:1961Natur.191..864.. doi: 10.1038/191864b0 . S2CID   38045877.
  4. Penicillium islandicum causes hepatic necrosis and has carcinogenic properties
  5. Kohei Mizutani; Yusuke Hirasawa; Yoshiko Sugita-Konishi; Naoki Mochizuki; Hiroshi Morita (2008). "Structural and conformational analysis of hydroxycyclochlorotine and cyclochlorotine, chlorinated cyclic peptides from Penicillium islandicum". J. Nat. Prod. 71 (7): 1297–1300. doi:10.1021/np800150m. PMID   18558744.
  6. 1 2 Schafhauser, Thomas; Kirchner, Norbert; Kulik, Andreas; Huijbers, Mieke M. E.; Flor, Liane; Caradec, Thibault; Fewer, David P.; Gross, Harald; Jacques, Philippe (2016-11-01). "The cyclochlorotine mycotoxin is produced by the nonribosomal peptide synthetase CctN in Talaromyces islandicus (Penicillium islandicum)" (PDF). Environmental Microbiology. 18 (11): 3728–3741. doi:10.1111/1462-2920.13294. ISSN   1462-2920. PMID   26954535. S2CID   22896792.
  7. Gosh, Anil; Manmade, Awinash; Townsend, James; Bousquet, Ann; Howes, John; Demain, Arnold (June 1978). "Production of Cyclochlorotine and a New Metabolite, Simatoxin, by Penicillium islandicum Sopp". American Society for Microbiology. 35 (6): 1074–1078. doi:10.1128/AEM.35.6.1074-1078.1978. PMC   242987 . PMID   677874.