Aflatoxin biosynthesis in Aspergillus parasiticus: effect of methionine analogs

The physiological effects of DL-ethionine and related methionine analogs upon cellular protein synthesis and methyl group transfer to aflatoxin B1 in Aspergillus parasiticus were examined in growing and resting cell systems. The addition of DL-ethionine (0.02 M) to growing mycelia inhibits cellular growth some 37% after 120 h of development. Addition of ethionine before 50 h prevents any aflatoxin synthesis; however, addition of ethionine after aflatoxin production begins has little effect upon continued synthesis. The enzymes responsible for aflatoxin production are made during the transitional phase of growth (50–70 h). During this period, ethionine administration blocks protein synthesis (measured by 14C-methionine incorporation) 85% and prevents aflatoxin synthesis. Since exogenous ethionine (3.2 mM) inhibits aflatoxin B1 synthesis about 50%, a competitive-type inhibition is indicated. Such inhibition is accompanied by the formation of a new aflatoxin B1 derivative. The incorporation of 14C-ethyl-ethionine into this derivative indicates a transethylation of the toxin ring system in the formation of ethoxy-aflatoxin B1. The addition of DL-ethionine and S-ethylcysteine to proliferating cells yields some of the aflatoxin B1 derivative.