Aflatoxin Biosynthetic Pathway and Pathway Genes

Among the over 185 known species within the genus Aspergillus, Aspergillus flavus is the most economically important because it produces the toxic and carcinogenic aflatoxins. Its non-aflatoxigenic relative A. oryzae is used extensively for food fermentations (Jelinek et al., 1989). It is one of the most abundant soil-borne molds on earth. A. flavus fungus is a saprobe mold that is capable of surviving on many organic nutrient sources like plant debris, tree leaves, decaying wood, animal fodder, cotton, compost piles, dead insects and animal carcasses, stored grains, and even immunocompromised humans and animals (Klich, 1998). It has the ability to survive temperatures ranging from 12°C to 48°C, but the optimal growth temperature ranges from 28°C to 37°C. Its ability to grow at relatively high temperatures contributes to its pathogenicity toward humans and other warm blooded animals. For most of its lifecycle, the fungus exists in the form of mycelium or asexual spores known as conidia. Under adverse conditions such as lack of adequated nutrients or water, the fungal mycelium will transform to resistant structures called sclerotia which can survive extremely harsh environmental conditions. The fungus overwinters either as spores, sclerotia, or as mycelium in debris. When conditions become favorable the sclerotia germinate directly to produce new colonies or conidiophores with conidia (Bennett et al., 1986; Cotty, 1988; Chang et al., 2002). Aflatoxins were first identified as the cause of a severe animal poisoning incident in England in 1960 called the Turkey X disease (Allcroft et al., 1961; Lancaster et al., 1961). A. flavus produces aflatoxin B1 and B2 whereas A. parasiticus, produces aflatoxins B1, B2, G1, and G2. These four major aflatoxins are named based on their blue (B) or green (G) fluorescence under ultraviolet light, and their relative mobility by thin-layer chromatography on silica gel. Aflatoxin M1 is a hydroxylated derivative metabolized from aflatoxin B1 by cows and secreted in milk (Van Egmond, 1989). In addition to aflatoxins B1 and B2, A. flavus also produces many other mycotoxins such as cyclopiazonic acid, kojic acid, beta-nitropropionic acid, aspertoxin, aflatrem and aspergillic acid (Goto et al., 1996). The disease caused by ingestion of aflatoxins in contaminated food or feed is called aflatoxicosis. Acute aflatoxicosis occurs when aflatoxins are consumed at moderate to high levels. Depending on the level and duration of exposure, aflatoxins possess both hepatotoxic and carcinogenic properties. Symptoms in humans include vomiting, abdominal pain, alteration in digestion, limb and pulmonary edema, convulsions, rapid progressive jaundice,