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Table 14 Conflicts between EcoCyc–18.0–GEM growth predictions and experimental carbon source utilization data for aerobic growth on Biolog PM plates at 37°C

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

Carbon source

HT

Sim

Comments

Dextrins

+

General dextrin uptake and catabolism via glg is described in EcoCyc, but the system is not applied to the dextrins in EcoCyc–18.0–GEM because of MetaFlux’s current inability to model polymerization reactions.

Lactulose

+

Lactulose is taken up by the MelB melibiose transporter [153], although this route of uptake is not present in EcoCyc. Lactulose is capable of inhibiting LacY transport of o-nitrophenyl- β-D-galactopyranoside [154], and can be anaerobically fermented by E. coli[155], but the route of catabolism is unknown.

Methyl- α-D-galactopyranoside

+

Methyl- α-D-galactopyranoside is taken up via the MelB melibiose transporter [153], and is capable of inhibiting LacY transport of o-nitrophenyl- β-D-galactopyranoside [154]. The route of catabolism is unknown.

Methyl- β-D-galactoside

+

Methyl- β-D-galactoside is taken up via MglABC transporter or MelB transporter, but the catabolic pathway is unknown. It is capable of inhibiting LacY transport of o-nitrophenyl- β-D-galactopyranoside [154], and is reported as a substrate of LacZ [156]. Inside the cell, methyl- β-D-galactoside is acetylated by LacA galactoside acetyltransferase [157], after which its fate is unclear.

Methyl pyruvate

+

Methyl pyruvate is a competitive inhibitor of the active pyruvate transport system [158]. No route of uptake for methyl pyruvate is present in EcoCyc, and the route of catabolism is unknown.

Melibionate

+

These compounds’ route of uptake is unknown.

1-O-methyl- β-D-glucuronate

+

 

3-O- β-D-galactopyranosyl-D-arabinose

+

 

Methyl D-lactate

+

 

Mono-methyl hydrogen succinate

+

 

L-galactono-1,4-lactone

+

The route of uptake is unknown; it may be catabolized via a ring opening to L-galactonate, as with D-galactono-1,4-lactone.

Meso-tartrate

+

PM experiments indicate that meso-tartrate can be used as a carbon source by E. coli, in contradiction of the reports of [159] and [160]. meso-tartrate is not associated with L/D-tartrate uptake processes in EcoCyc.

Bromosuccinate

+

Bromosuccinate is described in the literature is as an irreversible inhibitor of aspartate transcarbamylase [161] and it may be taken up via the same pathways as aspartate. No route of uptake is present in EcoCyc.

2-hydroxybutyrate

+

The route of uptake is unknown.

Citrate

+

Most strains of E. coli cannot use citrate as a carbon source under aerobic conditions because of lack of transporter expression [162]; the citrate/succinate antiporter CitT is expressed under anaerobic conditions, although a cosubstrate is still required to generate reducing power to form succinate [163]. MetaFlux does not currently model gene regulation.

Putrescine

+

These nitrogenous compounds cannot be used as carbon sources under the high-nitrogen

4-aminobutyrate

+

conditions of the Biolog PM carbon source assay, given the lack of Ntr-mediated expression

Ornithine

+

of their catabolic pathways [164]. MetaFlux does not currently model gene regulation.

L-arginine

+

Arginine cannot be used as a carbon source by E. coli K–12 because of the absence of induction and transport [165, 166]. MetaFlux does not currently model gene regulation.

Cellobiose

+

Cellobiose cannot be used as a carbon source by E. coli K–12 because of its inability to abolish repression of the ChbABC chitobiose/cellobiose PTS permease system by NagC [167, 168]. MetaFlux does not currently model gene regulation.

Glycine

+

Biolog PM experiments employing glycine as a carbon source return a consensus no-growth result, but EcoCyc–18.0–GEM predicts that glycine can be used as a carbon source via assimilation into 5,10-methyltetrahydrofolate by the glycine cleavage system. This is a wasteful pathway, producing one CO 2 and one molecule of 5,10-THF per glycine molecule taken up. We found no information on conventional growth experiments assaying the ability of E. coli K–12 to use glycine as a carbon source.

D-tartrate

+

D-tartrate does not support growth under aerobic conditions in the experiments of [160]. It uses the anaerobic TtdT transporter in EcoCyc–18.0–GEM; the DcuB transporter may be the correct route of entry for D-tartrate under anaerobic conditions [159].

Ethanolamine

+

E. coli requires a source of cob(I)alamin for catabolism of ethanolamine by the adenosylcobalamin-dependent ethanolamine ammonia-lyase [169172]. MetaFlux does not currently model enzyme cofactor requirements.

  1. Column headings are as follows: < Element > Source: Nutrient source under test. HT: High-throughput experiment. Sim: Simulation. Column entries are as follows: +: Nutrient can support growth. –: Nutrient cannot support growth. For example, D-fructose supports growth according to the consensus of experimental aerobic Biolog PM assays recorded in EcoCyc, but EcoCyc–18.0–GEM predicts that it does not support growth.