Organic acids: Old metabolites, new themes

Fumaric, L-malic and citric acids are intermediates of the oxidative tricarboxylic acid (TCA) cycle which in eukaryotes is localized in mitochondria. These organic acids are synthesized and accumulated in the medium to very high concentrations by filamentous fungi such as Aspergillus spp. and Rhizopus sp. This article reviews basic research on the unusual acid production capability and the associated metabolic pathways operating under defined stress conditions in these specific fungi. In particular, we describe and discuss the importance of the cytosolic reductive TCA pathway, which includes the cytosolic activities of pyruvate carboxylase, malate dehydrogenase and fumarase, for production of fumaric and L-malic acids. This article also describes the differences between fumaric acid, L-malic acid and citric acid production by different organisms (filamentous fungi, yeast, and higher eukaryotes), and the possible application of novel technologies (genetic engineering and bioinformatics) to fungal systems which may offer new industrial potential of filamentous fungi for the production of valuable metabolites.