Figure 8

VeA controls intracellular carbon flow in Aspergillus parasiticus. The schematic illustrates compartmentalization of biosynthesis of secondary metabolites, branched chain amino acid catabolism, and biosynthesis of ethanol in Aspergillus. Acetyl-CoA is produced in the mitochondrion, the peroxisome and in the cytoplasm; acetyl-CoA is the precursor of aflatoxin and other secondary metabolites [4]. Early steps in aflatoxin biosynthesis occur in peroxisomes [22]; the middle and late steps take place in aflatoxisomes [4, 12]. The biosynthesis and catabolism of branched chain amino acids occur in the mitochondrion; branched chain acyl-CoAs serve as the precursors of branched chain acids, branched chain alcohols and branched chain esters. Acyl-CoA and acetyl-CoA serve as the precursors of the unknown polyketide X. Ethanol is produced through nonoxidative decarboxylation of pyruvate followed by conversion of acetaldehyde to ethanol by alcoholdehydrogenase; acety-CoA may also be converted to ethanol. VeA negatively regulates branched chain amino acid catabolism and ethanol biosynthesis. In addition, VeA is a positive regulator of β-oxidation of fatty acids in mitochondria and peroxisomes during the late stages of stationary phase. When secondary metabolism is blocked in ΔveA, carbon flow is re-directed to elevated ethanol production and branched chain amino acid-derived volatiles. Overall, VeA is "a master-coordinator", which plays a role in regulation of carbon flow through metabolic processes (primary and secondary) in different cellular compartments. Known metabolic and regulatory pathways are shown by solid lines; hypothesized pathways are indicated by dashed lines. Abbreviations: BCAA, branched chain amino acids; PM, plasma membrane.