Peptidic mycotoxins

Erase et ai, The Chemistry of Mycotoxins, Progress in the Chemistry of Organic Natural Products, Vol. 91, DOI 10.1007/978-3-7091-1312-7 15, 

Peptidic mycotoxins are, among others, produced by Aspergillus, Fusarium, Penicillium, Pithomyces, and Trichoderma 10). 

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Mikami Y, Fukushima K, Arai T, Abe F, Shibuya H, Ommunra Y. Leucinostatins, peptide mycotoxins produced by Paecilomyces lilacinus and their possible roles in fungal infections. Zbl Bakt Hyg 257 275-283, 1984. 

A considerable number of mycotoxins that show high toxicity to vertebrates and/ or invertebrates are produced by organisms associated with crop plants (Flannigan 1991). There are many known cases of human poisoning caused by such compounds. There are three broad categories of mycotoxins represented here, based on the structures of the intermediates from which these secondary metabolites are derived. They are (1) compounds derived from polyketides, (2) terpenes derived from mevalonic acid, and (3) cyclic peptides and derivatives thereof. 

Drugs, alkaloids, mycotoxins, amino acids, flavinoids, heterocyclic compounds, lipids, steroids, organic acids, terpenes, vitamins. Proteins, peptides, surfactants. 

Tenuazonic acid has a broad toxicity spectrum and is regarded as a mycotoxin [28]. It was first detected as a growth inhibitor of tumour cells (human adenocarcinoma), and was later shown to have weak antibacterial and, at high dose levels (100-500 p,g/ml), antiviral activity towards poliovirus MEF-1, enterovirus (ECHO-9), respiratory viruses (parainfluenza-3), vaccinia and Herpes simplex (HF). It has been shown to be an inhibitor of peptide bond formation in preventing substrate binding to acceptor site of peptidyltransferase in human ribosomes [29]. 

The third mechanism is peritubular extraction of peptides and proteins from postglomerular capillaries and intracellular metabolism. Experiments using iodi-nated growth hormone (125I-rGH) have demonstrated that, while reabsorption into endocytic vesicles at the proximal tubule is still the dominant route of disposition, a small percentage of the hormone may be extracted from the peritubular capillaries [79, 86]. Peritubular transport of proteins and peptides from the baso-lateral membrane has also been shown for insulin [87] and the mycotoxin ochra-toxin A [88]. 

Chemical-induced liver injury is encountered in a variety of circumstances. Some natural toxins such as the peptides of Amanita phalloides, the pyrrolizidine alkaloids, the toxin of the cycad nut, and other plant toxins are hazards posed by the environment. Some mycotoxins are ingested unknowingly because of feed contamination due to climatic conditions favorable to fungal growth. Other circumstances of exposure to hepatotoxins include contamination of water supply with cyanobacterial toxins, which led to the tragic death of 60 patients in a hemodialysis clinic in Brazil in 1996 (Jochimsen et al, 1998). 

Aflatoxins, alkaloids, anabolic compounds, barbiturates, benzodiazepines, bile add, carbohydrates, etheric oil components, fatty adds, flavanoids, glycosides, lipids, mycotoxins, nitroanilines, nucleotides, peptides, pestiddes, steroids, sulfonamides, surfacfanfs, sweef-eners, tetracyclines, vitamins... 

Rhizopus microsporus strains have also been described as a source of food mycotoxins. Rhizonins, such as 93 (Scheme 11), which were the first-described toxins from zygomycetes, are strongly hepatotoxic nonribosomal peptides isolated from moldy peanuts in Mozambique. Examination for the presence of bacteria again showed that a Burkholderia sp. endosymhiont is the true biosynthetic source.As with the rhizoxin (28) producer, the establishment of a pure symbiont culture was successful. 

Penicillium islandicum is a chlorine-containing peptide whose structure was determined later. This organism also produced cyclochlorotine (92), which is an infectant of yellowed rice [133], The fungus Metarhizium anisopliae produces the chlorohydrin cyclic peptide (93) [134], Cyclochlorotine, a hepatotoxic mycotoxin, was also isolated from Penicillium islandicum. 

The smallest cyclic peptides built from amino acids are the so-called diketopiperazines (DKP). In recent research, the DKPs and higher functionalized analogs - the thiodiketopiperazines (TDKP) - have become attractive due to their broad biological activity (390). The DKP or TDKP moiety can be found in a great variety of mycotoxins. Both DKPs and TDKPs can, for example, be isolated from Aspergillus, Candida, Chaetomium, Gliocladium, Penicillium, and Verticillium species (7, 390). The most common structural motifs A-D of this class of compounds are depicted in Fig. 10.1. Many of these natural products show C2 symmetry, which means they consist of two identical amino acids (R = R in Fig. 10.1). 

See also Carbohydrates Overview. Extraction Solid-Phase Extraction Supercritical Fluid Extraction. Food and Nutritional Analysis Sample Preparation Antioxidants and Preservatives Mycotoxins Oils and Fats. Lip-Ids Overview. Peptides. Proteins Overview. Toxins Mycotoxins Neurotoxins. Vitamins Overview Fat-Soluble Water-Soluble. 

Biomolecules labeled with (aUcyne)[Co2(CO)g] entities are among the most widely studied molecules in bioorganometallic chemistry, thanks to their ease of preparation and reasonable stabiUty [96], It is thus no surprise that the Uterature provides examples of peptides [97, 98], proteins [99], therapeutic drugs [100], abortifacient medications such as RU486, 35 [101], corticoids and androgens [102], methotrexate 37 [103], the mycotoxin zearalenone 36 [104, 105], estrogens [106-110] and pesticides [111] modified by this entity (Scheme 3.15). 

Toxins are natural venoms produced by the metabolic activities of living organisms. These compounds can be small molecules, peptides, or proteins and are capable of causing damage when introduce into the body. This definition includes a wide range of molecules with different structure and activity, such as mycotoxins, produced by fungus marine toxins, produced by dinoflagellates and venoms (peptidic toxins) secreted by some animals, such as snakes, scorpions, and bees. 

From a toxicological point of view, the most important representative of this group of mycotoxins is ochratoxin A, 3R)-N-[(5-chloro-3,4-dihydro-8-hydroxy-3-methyl-1-0X0-lH-2-benzo-pyran-7-yl)carbonyl]-L-phenylalanine (12-92), the molecule of which phenylalanine JV-substituted with a derivative of 3R)-3,4-dihydro-3-methylisocoumarine that contains at C-5 a chlorine atom to which are attributed the toxic effects of ochratoxin A. The incorporation of the chlorine atom into the skeleton of ochratoxin A is done by the action of chloroperoxidase the chlorine donor is inorganic chloride. Ochratoxin B (12-92) differs from ochratoxin A only in the absence of the chlorine atom, while ochratoxin C (12-92) is an ethyl ester of ochratoxin A. Ochratoxins a, p and y resulting from from parent compounds by the loss of phenylalanine caused by peptide bond hydrolysis, are virtually non-toxic, in addition to ochratoxin B, and are not routinely monitored. 

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