Roquefortine C Explained

Roquefortine C is a mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines^[1] produced by various fungi, particularly species from the genus Penicillium.^[2] It was first isolated from a strain of Penicillium roqueforti, a species commercially used as a source of proteolytic and lipolytic enzymes during maturation of the blue-veined cheeses, Roquefort, Danish Blue, Stilton and Gorgonzola.

Roquefortine C is a cyclodipeptide mycotoxin derived from the diketopiperazine cyclo(Trp-dehydro-His) and is a relatively common fungal metabolite produced by a number of Penicillium species. It is also considered one of the most important fungal contaminants of carbonated beverages, beer, wine, meats, cheese and bread.^[3] At high doses roquefortine C is classified as a toxic compound.^[4] Although it is a potent neurotoxin^{[5] [6]} at high doses, at low concentrations of 0.05 to 1.47 mg/kg that occur in domestic cheeses, it was found to be "safe for the consumer".^[7] The mechanisms underlying its toxicity and metabolism have been investigated by studying its interaction with mammalian cytochrome P450 enzymes. In addition to these toxic properties, roquefortine C reportedly possesses bacteriostatic activity against gram-positive bacteria,^[8] but only in those organisms containing haemoproteins.^[9]

Roquefortine C contains the unusual E-dehydrohistidine moiety, a system that typically undergoes facile isomerization under acidic, basic, or photochemical conditions to isoroquefortine C, the 3,12 double-bond Z-isomer of roquefortine C.^[10] However isoroquefortine C is not a natural product and in contrast to roquefortine C does not bind iron. Both have been synthesised.

Related compounds

• Aristolochene
• Aflatoxin
• Patulin

External links

• Roquefortine C on https://www.scbt.com

Notes and References

1. 2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products . Borthwick AD . Chemical Reviews . 2012 . 112 . 7 . 3641–3716 . 10.1021/cr200398y . 22575049.
2. Kokkonen M, Jestoi M, Rizzo A . The effect of substrate on mycotoxin production of selected Penicillium strains . International Journal of Food Microbiology . 99 . 2 . 207–14 . 2005 . 15734568 . 10.1016/j.ijfoodmicro.2004.08.014 .
3. Borthwick AD, Da Costa NC . 2,5-Diketopiperazines in Food and Beverages: Taste and Bioactivity . Critical Reviews in Food Science and Nutrition . 57 . 4 . 718–742 . 2017 . 25629623 . 10.1080/10408398.2014.911142. 1334464 .
4. Aninat C, Hayashi Y, André F, Delaforge M . Molecular requirements for inhibition of cytochrome P450 activities by roquefortine . Chemical Research in Toxicology . 14 . 9 . 1259–1265. July 2001 . 11559041 . 10.1021/tx015512l .
5. SCBT . Roquefortine - A potent neurotoxin produced most notably by Penicillium species .
6. EPA . Penicillium roqueforti Final Risk Assessment .
7. Finoli C, Vecchio A, Galli A, Dragoni I . Roquefortine C occurrence in blue cheese. . 11271775 . 64 . 2 . February 2001 . J. Food Prot. . 246–51 . 10.4315/0362-028x-64.2.246. free .
8. Kopp-Holtwiesche B, Rehm HJ . Antimicrobial action of roquefortine . Journal of Environmental Pathology, Toxicology and Oncology . 10 . 1–2 . 41–44. December 1989 . 2231314 .
9. Aninat C, Andre F, Delaforge M . Oxidative metabolism by P450 and function coupling to efflux systems: modulation of mycotoxin toxicity . Food Additives and Contaminants . 22 . 4 . 361–368. April 2005 . 16019806 . 10.1080/02652030500073287 . 9880652 .
10. Shangguan N, Hehre WJ, Ohlinger WS, Beavers MP, Joullie MM . The total synthesis of roquefortine C and a rationale for the thermodynamic stability of isoroquefortine C over roquefortine C . Journal of the American Chemical Society . 130 . 19 . 6281–6287. April 2008 . 18412344 . 10.1021/ja800067q .