Metabolic modeling of acetyl-CoA mutants of Aspergillus nidulans.

Jessica H. Marshall, Harvey W. Blanch and Jay D. Keasling


Aspergillus species produce many secondary metabolites including the toxic, carcinogenic polyketide compounds aflatoxin (AF) and its precursor sterigmatocystin (ST). AF and ST are synthesized from acetyl-CoA. Mutations in genes associated with acetyl-CoA metabolism can dramatically affect the amount of ST produced in A. nidulans (N. Keller, personal communication). We are using metabolic modeling techniques, specifically metabolic flux and isotopomer analyses, to characterize the flow of carbon through primary and secondary metabolism in these mutant A. nidulans strains. Metabolic flux analysis calculates the metabolic fluxes through all reactions included in an organism's metabolic network, and thus allows quantification of the effect of genetic manipulations or changes to growth conditions on the entire metabolic network. In isotopomer analysis, 13C-labeled glucose is fed to the cells, and the label pattern of metabolites such as amino acids is measured and used as model input to improve flux calculations. Here we present flux calculations obtained from our model using measurements of steady-state biomass composition and amino acid 13C label distribution from continuous cultures of A. nidulans as inputs.

abstract No: 

Fungal Genet. Newsl. 50 (Supl):abstract

Full conference title: 

22nd Fungal Genetics Conference
    • Fungal Genetics Conference 22nd (2001)