Organic acids: old metabolites, new themes

Abstract

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.

Microbial growth in Acrocomia aculeata pulp oil, Jatropha curcas oil, and their respective biodiesels under simulated storage conditions

“…Overall, the changes in pH in the aqueous phase could indicate the production of metabolites of acidic nature in quantities sufficient to overcome the buffering capacity of the mineral minimum medium. Beside the metabolic products formed during the fungal development, a reduction in the pH as a result of the treatments performed could be related to cellular lysis, polymeric products, and production of organic acids (Bento et al, 2005;Goldberg et al, 2006). Thus, one could conclude that by prolonging the cultivation period and without any limitations on oxygen and nutrients, the fungal isolates used in this work could have produced more metabolites which could have in turn led to a greater reduction in pH.…”

Organic acid production in Aspergillus niger and other filamentous fungi

“…In summary, the reaction kinetics of FumR favour the conversion of fumarate to L-malate rather than the reverse direction, and FumR activity of acid-producing mycelium is completely blocked in the presence of 2 mM fumarate (note that the data on FumR inhibition have never been published, but that this finding is cited by Goldberg et al (2006); Meussen et al (2012). This suggests the presence of an alternative pathway that is responsible for fumarate accumulation in R. delemar.…”

“…The filamentous fungus Rhizopus delemar, on the other hand, secretes relatively high amounts of fumarate, and before the establishment of fumarate production via chemical conversion, Rhizopus spp were used as biological fumarate producers (Goldberg et al, 2006). In contrast to A. niger, however, R. delemar is regarded as opportunistic human pathogen with an aggressive course of infection, and its genetic makeup (Ma et al, 2009) makes it unsuitable for genetic modification.…”

“…Fungal fumarate accumulation, however, is attributed to enzymes of the rTCA cycle in the cytosol (Goldberg et al, 2006;Wright et al, 1996).…”

“…Amongst the microorganisms identified to be natural fumarate producers, the filamentous fungus Rhizopus delemar has the highest product yields (Foster and Waksman, 1939a). The most important factor influencing fumarate production in R. delemar is a high carbon:nitrogen ratio; extracellular fumarate accumulation happens after the growth phase, and especially when the nitrogen in the medium has been depleted (Goldberg et al, 2006;Magnuson and Lasure, 2004). The choice of nitrogen source has been reported to influence the final fumarate yield (Foster and Waksman, 1939a;Rhodes et al, 1959;Zhang et al, 2007), but so far no consensus on these influences has been reached.…”