Mycotoxins ergot alkaloids

Mycotoxins of most interest are those found in human food or in the feed of domestic animals. They include the ergot alkaloids produced by Claviceps sp aflatoxins and related compounds produced by Aspergillus sp and the tricothecenes produced by several genera of fungi imperfecti, primarily Fusarium sp. 

The mycotoxins with the greatest potential risk to human and animal health as food and feed contaminants are AFs, trichothecenes, fiimonisins, zearalenone, ochratoxin A, and ergot alkaloids.109 Other mycotoxins such as cyclopiazonic acid, sterigmatocystin, gliotoxin, citrinin, penitrems, patulin, fusarin C, penicillic acid, and PR... 

It is difficult to conceive that even poisons can be harnessed as medically-useful drugs, yet this is the case with the ergot alkaloids. These mycotoxins (i.e., toxins produced by molds) were responsible for fatal poisoning of humans and animals (ergotism) throughout the ages after consumption of bread made from grain contaminated with species of... 

The amino acid tryptophan is a precursor of several fungal metabolites that affect the central nervous system. We have already met it as a constituent of the ergot alkaloids. Roquefortine (9.25) is a metabolite of Penicillium roqueforti and P. camemberti, which are found on some cheeses. Roquefortine is one of a series of mycotoxins that affect the central nervous system and induce tremors. The more complex penitrems are tremorogenic neurotoxins that are produced by the P. crustosum series. They are biosynthesized from a tryptophan and a triterpene unit. 

Ergot alkaloids are mycotoxins produced (mainly) by Claviceps species which have deleterious effects on the central nervous system of mammalia on the other hand, they have a long biotechnological tradition with manifold applications in therapy of human central nervous system (CNS) disorders (for reviews, see Keller and Tudzynski, 2001 Tudzynski et al., 2001). Chemically they are 3,4-substituted indole derivatives having a tetracyclic ergoline ring structure (Fig. 2). 

Examples of mycotoxins include the ergot alkaloids produced when the ergot fungus grows on rye (responsible for outbreaks of a disease called ergotism, or St Anthony s Fire), trichothecanes produced by Fusarium species (associated with alimentary toxic aleukia fatalities in the Second World War) and the aflatoxins. 

In the 1980s Muratake and Natsume (202) in a number of reports presented a new, interesting approach to the synthesis of substituted indole derivatives that focused on their use as intermediates in the preparation of a variety of clavine alkaloids and mycotoxins. The method elaborated by the authors consisted of constructing the specifically substituted benzene portion of the indole nucleus, with 1-methoxycarbonylpyrrole being the starting material. The functionalized 4-alkylindole thus obtained was transformed to a tricyclic indole derivative which appeared to be a common intermediate for the synthesis of several ergot alkaloids, as exemplified by the synthesis of ( )-dihydrosetoclavine (203-205) (Scheme 42). Recently, the application of this method was extended by the authors (206) to the syntheses of a series of marine alkaloids, the hapalindoles. Most of these alkaloids have a tetracyclic framework made up of 3,4-substituted tryptamine and two isoprene units. 

Neurotoxic mycotoxins of the indole alkaloid type from many mold fungi of the genus Penicillium. e.g., P. roqueforti. P cyclopium, P. commune, P crustosum, P. chrysogenum, P. griseofulvum. The R. occur in blue cheese and cotton seeds and have also been found in beer. The main alkaloid is R. C. R. can lead to abortions in animal experiments. Today, toxin-free strains are used for the production of cheese. R. C and R. D are formed from tryptophan, histidine (diketopipera-zine part) and mevalonic acid. R. A and R.B are alkaloids of the clavine type (see ergot alkaloids). The LD50 for mice (i.p.) is 15 mg R.C/kg. 

Reinhard H, Rupp H, Zoller O. Ergot alkaloids quantitation and recognition challenges. Mycotoxin Res 2008 24(1) 7-13. 

TLC, together with analytical features (plate material, elution, detection/visualization, limit of detection). Of particular interest are the following products aflatoxins Bl, B2, Gl, and G2, zearalenon, ochratoxin, and fiimo-nisins B1 and B2 in maize. Recently, high-performance TLC (HPTLC) techniques have also been applied to forage samples commonly infected with an endophyte considered as symbiotic but responsible for disorders in animals. These mycotoxins include lolitrems and ergot alkaloids. 

Scott PM (2007) Analysis of ergot alkaloids - a review. Mycotoxin Res 23 113-121... 

Ruhland M, Tischler J (2008) Determination of ergot alkaloids in feed by HPLC. Mycotoxin Res 24 73-79... 

Sulyok et al. [113] reported the first validated method for the determination of 39 mycotoxins in wheat and maize by liquid chromatography with electrospray ionization-triple quadmpole mass spectrometry (LC/ESI-MS/MS) without the need for any cleanup. The 39 analytes included A and B trichothecenes (including deoxynivalenol-3-glucoside), ZEN and related derivatives, fumonisins, enniatins, ergot alkaloids, ochratoxins, aflatoxins, and moniliformin, and six trichothecene mycotoxins (NIV, DON, fusarenon-X, 15-acetyldeoxynivalenol, 3-acetyldeoxynivalenol, and T-2 toxin). 

For LC-MS separation with highly specific detection methods simple extraction procedures and filtration can be followed by direct injection into the LC-MS. Extraction with methanol/water acidified with formic acid and subsequent ultrafil-tration with a 30 kD filter has been used with success. Similarly simple approaches form the basis of most multi-mycotoxin methods which determine several ergot alkaloids along with other mycotoxins. 

Multianalyte methods used to measure substantial numbers of mycotoxins in feed and food have often included ergot alkaloids [12, 33-35]. A multianalyte LC-MS/MS method without cleanup has been used to measure 87 different mycotoxins including 25 ergot alkaloids with LODs of 0.02-1.2 pg kg . A similar approach has been used to perform a semiquantitative survey that included all 12 of the major C. purpurea ergot alkaloids and also another 12 other ergot alkaloids from different other Claviceps species. 

Heat treatment of contaminated materials decreases mycotoxin concentrations in many cases. Aflatoxins are especially thermostable and a significant decrease in their content occurs at temperatures of about 200 °C. Ergot alkaloids and zearalenone are also very stable at high temperatures. 

---