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Table 8 False gene essentiality predictions within glycolytic and TCA cycle metabolism

From: A genome-scale metabolic flux model of Escherichia coli K–12 derived from the EcoCyc database

Gene HT Sim Conv Citations Comments
aceE + + [32, 36, 5557] Baba et al. [32] observe aceE null mutant growth to OD600 0.353 (nonessential), aceF null mutant
aceF +   growth to OD600 0.091 (the line of loose essentiality), and lpd null mutant growth to OD600 0.061
lpd +   (loose essential). Langley and Guest [55] observe pyruvate dehydrogenase complex essentiality and [56, 57] discuss it in the context of poxAB; [36] suggest mutants overexpressing pyruvate oxidase allow growth on glucose.
eno + [36, 58, 59] Hillman and Fraenkel [58] describe gapA essentiality and [59] describes eno/gapA/pgk
gapA +   essentiality. Null mutants in these enzymes suffer from glucose toxicity because of glucose
pgk +   catabolite repression of other carbon utilization pathways. See also [36].
icd + [32, 36, 6067] EcoCyc–18.0–GEM icd deletion mutants grow via condensation of propionyl-CoA and glyoxylate to 2-hydroxyglutarate [60, 61], and oxidation of 2-hydroxyglutarate to 2-oxoglutarate via LhgO [66]. icd is broadly essential on minimal glucose media in [32]. icd deletion mutants require glutamate [62, 63] and can grow on LB [64, 65], although [67] reports growth on M9 minimal media. See also [36].
fbaA + [36, 6871] The class I fructose bisphosphate aldolase fbaB is listed as an isozyme for fbaA in EcoCyc, but is expressed only under gluconeogenic conditions [68, 69]. Use of the fsa/dhaK pathway [70, 71] to substitute for fbaA appears to be blocked in the results of [32] by lowered dhaK expression in E. coli with operational phosphotransferase systems. Other effects of fbaA deletion are discussed in [36].
gltA + [36, 72, 73] PrpC, the 2-methylcitrate synthase in the propionate utilization pathway, is an isozyme for the GltA citrate synthase. prpC is conditionally expressed in the presence of propionate. Discussed in [36, 73].
pfkA + [32, 36, 74, 75] pfkA and pfkB are listed as isozymes for the 6-phosphofructokinase reaction, but PfkB activity is insufficient to allow strong growth in vivo in the absence of pfkA according to [74]. pfkA is loosely essential (OD600 0.087) in [32]. See [36] and [75], which indicate that both pfkA and pfkB must be deleted to block growth.
ppc + + [32, 76, 77] Peng et al.[76] demonstrate growth of ppc deletion mutants without detectable Ppc activity on M9 glucose minimal media. ppc grows on rich media but is narrowly essential under minimal glucose conditions in the high-throughput assay of [32]. EcoCyc–18.0–GEM ppc deletion mutants grow via activation of the glyoxylate shunt, in agreement with the observations of [76]. Patrick et al.[77] identified overexpression of the osmoregulatory system regulator EcfM and the uncharacterized protein YccT as capable of rescuing ppc deletion mutants.
tpiA + + [32, 36, 78, 79] Kim and Copley [36] describe tpiA essentiality based on methylglyoxal formation in tpiA null mutants, and the tpiA nonessentiality result of [32] as based on methylglyoxal pathway-expressing mutants [78, 79].
  1. The three available pathway options for navigating the route from glucose to the TCA cycle make up the superpathway of glycolysis, the pentose phosphate pathway and the Entner-Doudoroff pathway. Without modeling of regulation, product inhibition, and metabolite toxicity, the multiple re-entry points in the superpathway and the reversible nature of the pentose phosphate pathway allow carbon flux to route around deletions with weak growth. EcoCyc–18.0–GEM consequently produces several false positive results for these pathways. This set of genes has previously been discussed at length by [36]. The aceE and tpiA genes identified as essential in Figure two of [36] are judged nonessential by [32] and consequently by [6], and were predicted as nonessential by EcoCyc–18.0–GEM, but these nonessentiality conclusions appear incorrect based on conventional experiments described in the literature, and are thus included in this table. The converse is true for ppc, which is considered essential by high-throughput experiments, but is not essential in conventional experiment. See Table 7 caption for a description of column headings.