The biosynthesis of the aflatoxins.

These observations could be explained by sequestration of selenium in the form of selenomethionine and/or other selenoamino acids incorporated into the primary structure of proteins throughout the body.

T1 - Cloning of a gene associated with aflatoxin B1 biosynthesis in Aspergillus parasiticus

Aflatoxin, which is more toxic to rats than to mice, both as an acute poison and as a carcinogen, is transported more slowly into the liver cells and is metabolized more rapidly in the mouse than in the rat (Portman et al., 1970).


Biosynthesis of polyketides and related compounds.

Conversion of norsolorinic acid and other hypothetical intermediates into aflatoxin B1

Transferases are a group of enzymes that catalyze Phase 2 reactions. They conjugate xenobiotics with endogenous compounds such as glutathione, amino acids, glucuronic acid or sulphate.


PRODUCTION OF AFLATOXINS IN SUBMERGED CULTURE.

Sterigmatocystin is a penultimate precursor of aflatoxins and also a toxic and carcinogenic substance produced by many species, including Aspergillus nidulans.

Mutant of Aspergillus flavus producing more aflatoxin B2 than B1.

Recently, the majority of the enzyme reactions involved in aflatoxin/sterigmatocystin biosynthesis have been clarified, and the genes encoding the enzymes have been isolated.

High aflatoxin production on a chemically defined medium.

Aspergillus flavus isolates produce only aflatoxins B1 and B2, while Aspergillus parasiticus and Aspergillus nomius produce aflatoxins B1, B2, G1, and G2. Sequence comparison of the aflatoxin biosynthesis pathway gene cluster upstream from the polyketide synthase gene, pksA, revealed that A. flavus isolates are missing portions of genes (cypA and norB) predicted to encode, respectively, a cytochrome P450 monooxygenase and an aryl alcohol dehydrogenase. Insertional disruption of cypA in A. parasiticus yielded transformants that lack the ability to produce G aflatoxins but not B aflatoxins. The enzyme encoded by cypA has highest amino acid identity to Gibberella zeae Tri4 (38%), a P450 monooxygenase previously shown to be involved in trichodiene epoxidation. The substrate for CypA may be an intermediate formed by oxidative cleavage of the A ring of O-methylsterigmatocystin by OrdA, the P450 monooxygenase required for formation of aflatoxins B1 and B2. Aflatoxins are toxic and carcinogenic contaminants of foods and feeds that frequently are responsible for health and economic concerns in many countries (3, 34). These metabolites are produced by several species of Aspergillus, including A. flavus and A. pseudotamarii, which produce aflatoxins B1 and B2, and A. parasiticus and A. nomius, which produce aflatoxins

& Marth, E.H., Growth and aflatoxin production in meats.

The section then provides two general overviews on toxicology at the mechanistic level. Mechanistically, modern toxicologists consider that all toxic effects manifest their first actions at the cellular level; thus, cellular responses represent the earliest indications of the body’s encounters with a toxic agent. It is further assumed that these responses represent a spectrum of events, from injury through death. Cell injury refers to specific processes utilized by cells, the smallest unit of biological organization within organs, to respond to challenge. These responses involve changes in the function of processes within the cell, including the membrane and its ability to take up, release or exclude substances; the directed synthesis of proteins from amino acids; and the turnover of cell components. These responses may be common to all injured cells, or they may be specific to certain types of cells within certain organ systems. Cell death is the destruction of cells within an organ system, as a consequence of irreversible or uncompensated cell injury. Toxic agents may cause cell death acutely because of certain actions such as poisoning oxygen transfer, or cell death may be the consequence of chronic intoxication. Cell death can be followed by replacement in some but not all organ systems, but in some conditions cell proliferation induced by cell death may be considered a toxic response. Even in the absence of cell death, repeated cell injury may induce stress within organs that compromises their function and affects their progeny.