C ₄ -Dicarboxylate Utilization in Aerobic and Anaerobic Growth

Abstract

C4-dicarboxylates and the C4-dicarboxylic amino acid l-aspartate support aerobic and anaerobic growth of Escherichia coli and related bacteria. In aerobic growth, succinate, fumarate, D- and L-malate, L-aspartate, and L-tartrate are metabolized by the citric acid cycle and associated reactions. Because of the interruption of the citric acid cycle under anaerobic conditions, anaerobic metabolism of C4-dicarboxylates depends on fumarate reduction to succinate (fumarate respiration). In some related bacteria (e.g., Klebsiella), utilization of C4-dicarboxylates, such as tartrate, is independent of fumarate respiration and uses a Na+-dependent membrane-bound oxaloacetate decarboxylase. Uptake of the C4-dicarboxylates into the bacteria (and anaerobic export of succinate) is achieved under aerobic and anaerobic conditions by different sets of secondary transporters. Expression of the genes for C4-dicarboxylate metabolism is induced in the presence of external C4-dicarboxylates by the membrane-bound DcuS-DcuR two-component system. Noncommon C4-dicarboxylates like l-tartrate or D-malate are perceived by cytoplasmic one-component sensors/transcriptional regulators. This article describes the pathways of aerobic and anaerobic C4-dicarboxylate metabolism and their regulation. The citric acid cycle, fumarate respiration, and fumarate reductase are covered in other articles and discussed here only in the context of C4-dicarboxylate metabolism. Recent aspects of C4-dicarboxylate metabolism like transport, sensing, and regulation will be treated in more detail. This article is an updated version of an article published in 2004 in EcoSal Plus. The update includes new literature, but, in particular, the sections on the metabolism of noncommon C4-dicarboxylates and their regulation, on the DcuS-DcuR regulatory system, and on succinate production by engineered E. coli are largely revised or new.

DcuA of aerobically grown Escherichia coli serves as a nitrogen shuttle (L‐aspartate/fumarate) for nitrogen uptake

“…Under anaerobic conditions, fumarate, L-malate or L-aspartate serve as electron acceptors in fumarate respiration, which produces succinate (see review by Kröger et al, 1992;Unden et al, 2016). Fumarate respiration requires C 4 -dicarboxylate/succinate antiport for the uptake of fumarate, L-malate or L-aspartate, which is coupled to the export of succinate (Engel et al, 1992;Janausch et al, 2002).…”

“…Only some of the physiological roles of DcuA are known (Six et al, 1994;Janausch et al, 2002;Unden et al, 2016). DcuA can support (anaerobic) fumarate respiration and C 4 -dicarboxylate/succinate antiport with either fumarate, L-malate or L-aspartate as the substrate (Six et al, 1994;Zientz et al, 1999).…”

Aspartate metabolism is involved in the maintenance of enterohaemorrhagic Escherichia coli O157:H7 in bovine intestinal content

“…In E. coli, aerobic uptake of aspartate is performed by the DctA transporter in symport with H + or Na + . Under anaerobiosis, DcuB is the most important fumarate/succinate antiporter, DcuA is able to catalyse antiport, uptake and efflux of C 4 -dicarboxylates and aspartate, and DcuC is the main succinate export carrier (Unden et al, 2016). In the mammal gut, E. coli strains that have access to oxygen probably use DctA symporter for aspartate uptake whereas another part of the bacterial population uses DcuA for antiporting of aspartate against succinate under oxygen-limited conditions.…”

Aerobic L-tartrate Utilization by Bacillus Isolates

“…When much preferred carbon sources like sugars and related derivatives are unavailable, bacteria utilize C 4 dicarboxylates as carbon sources commonly including succinate, L-malate, oxaloacetate or aspartate, either aerobically through citric acid cycle or anaerobically via fumarate respiration (fumarate used as an electron acceptor and reduced to succinate) 2 . Therefore, transporters, enzymes and regulations involved in C 4 -dicarboxylate metabolism under aerobic and anaerobic conditions are entirely different and have been extensively characterized in E. coli 3 .…”

“…Microbes including Aerobacter aerogenes, Clostridium sp., E. coli, Ruminococcus pasteurii and Ilyobacter tartaricus 4-6 catabolize tartrate anaerobically via tartrate dehydratase (EC 4.2.4.32), catalyzing the conversion of tartrate to oxaloacetate which gets further metabolized by fumarate respiration. In related bacterial species like Klebsiella, anaerobic tartrate utilization however occurs via a different route involving Na +dependent oxaloacetate decarboxylase 3 . Distinct dehydratases exist for each optical isomer, L-, Dand meso-tartrate, which are induced only by their specific substrates 4 .…”