Cyclopiazonic acid (
Names | |
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Preferred IUPAC name
(6aR,11aS,11bR)-10-Acetyl-11-hydroxy-7,7-dimethyl-2,6,6a,7,11a,11b-hexahydro-9H-pyrrolo[1′,2′:2,3]isoindolo[4,5,6-cd]indol-9-one | |
Identifiers | |
3D model (JSmol)
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707309 | |
ChEBI | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.162.058 |
EC Number |
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KEGG | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C20H20N2O3 | |
Molar mass | 336.391 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Cyclopiazonic acid is known to contaminate multiple foods because the molds that produce them are able to grow on different agricultural products, including but not limited to grains, corn, peanuts, and cheese.[2][5] Due to this contamination,
Chemically, CPA is related to ergoline alkaloids. CPA was originally isolated from Penicillium cyclopium and subsequently from other fungi including Penicillium griseofulvum, Penicillium camemberti, Penicillium commune, Aspergillus flavus, and Aspergillus versicolor. CPA only appears to be toxic in high concentrations. Ingestion of CPA causes anorexia, dehydration, weight loss, immobility, and signs of spasm when near death. CPA can be found in molds, corns, peanuts, and other fermented products, such as cheese and sausages.[6] Biologically, CPA is a specific inhibitor of SERCA ATPase in intracellular Ca2+ storage sites.[7] CPA inhibits SERCA ATPase by keeping it in one specific conformation, thus, preventing it from forming another.[8] CPA also binds to SERCA ATPase at the same site as another inhibitor, thapsigargin (TG). In this way, CPA lowers the ability of SERCA ATPase to bind an ATP molecule.[9]
Toxicity
editCases of
Biosynthesis
editThree enzymes are utilized in the biosynthesis of
Mechanism of Action of CpaS
editCpaS is made of several domains that belong either to the PKS portion or the NRPS portion of the 431 kDa protein.[2][3] The PKS portion is made up of three catalytically important domains and three additional tailoring domains that are common to polyketide synthases but not used in the biosynthesis of
Formation of β -CPA
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The second enzyme, CpaD, converts the cAATrp produced by CpaS to
Formation of α -CPA
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The final enzyme in the biosynthetic pathway, CpaO, converts
References
edit- ^ Holzapfel CW (March 1968). "The isolation and structure of cyclopiazonic acid, a toxic metabolite of Penicillium cyclopium Westling". Tetrahedron. 24 (5): 2101–19. doi:10.1016/0040-4020(68)88113-X. PMID 5636916.
- ^ a b c d e f g h i j k l m n Chang PK, Ehrlich KC, Fujii I (December 2009). "Cyclopiazonic acid biosynthesis of Aspergillus flavus and Aspergillus oryzae". Toxins. 1 (2): 74–99. doi:10.3390/toxins1020074. PMC 3202784. PMID 22069533.
- ^ a b c d e f Liu X, Walsh CT (September 2009). "Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-acetoacetyl-L-tryptophan". Biochemistry. 48 (36): 8746–57. doi:10.1021/bi901123r. PMC 2752376. PMID 19663400.
- ^ Seidler NW, Jona I, Vegh M, Martonosi A (October 1989). "Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum". The Journal of Biological Chemistry. 264 (30): 17816–23. doi:10.1016/S0021-9258(19)84646-X. PMID 2530215.
- ^ a b c d Nishie K, Cole RJ, Dorner JW (September 1985). "Toxicity and neuropharmacology of cyclopiazonic acid". Food and Chemical Toxicology. 23 (9): 831–9. doi:10.1016/0278-6915(85)90284-4. PMID 4043883.
- ^ Bullerman LB (2003). "MYCOTOXINS | Classifications". Encyclopedia of Food Sciences and Nutrition. pp. 4080–4089. doi:10.1016/B0-12-227055-X/00821-X. ISBN 978-0-12-227055-0.
- ^ Sosa MJ, Córdoba JJ, Díaz C, Rodríguez M, Bermúdez E, Asensio MA, Núñez F (June 2002). "Production of cyclopiazonic acid by Penicillium commune isolated from dry-cured ham on a meat extract-based substrate". Journal of Food Protection. 65 (6): 988–92. doi:10.4315/0362-028X-65.6.988. PMID 12092733.
- ^ Soler F, Plenge-Tellechea F, Fortea I, Fernandez-Belda F (March 1998). "Cyclopiazonic acid effect on Ca2+-dependent conformational states of the sarcoplasmic reticulum ATPase. Implication for the enzyme turnover". Biochemistry. 37 (12): 4266–74. doi:10.1021/bi971455c. PMID 9521749.
- ^ Ma H, Zhong L, Inesi G, Fortea I, Soler F, Fernandez-Belda F (November 1999). "Overlapping effects of S3 stalk segment mutations on the affinity of Ca2+-ATPase (SERCA) for thapsigargin and cyclopiazonic acid". Biochemistry. 38 (47): 15522–7. doi:10.1021/bi991523q. PMID 10569935.
- ^ Voss KA (May 1990). "In Vivo and In Vitro Toxicity of Cyclopiazonic Acid (CPA)". In Llewellyn GC, O'Rear CE (eds.). Biodeterioration Research: Mycotoxins, Biotoxins, Wood Decay, Air Quality, Cultural Properties, General Biodeterioration, and Degradation. Boston, MA: Springer US. pp. 67–84. doi:10.1007/978-1-4757-9453-3_5. ISBN 978-1-4757-9453-3.