Metabolic flux analysis of Escherichia coli ArcA and CreB mutants reveals shared control of carbon catabolism under microaerobic conditions of growth

Nikel, Pablo I.; Zhu, Jiangfeng; San, Ka‐Yiu; Galvagno, Miguel A.; Méndez, Beatriz S.; Bennett, George N

doi:10.1016/j.nbt.2009.06.791

Cited by 8 publications

(17 citation statements)

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“…Such factors could explain the low μ of creB mutants under microaerobic conditions. Higher Y X/S in creB mutants, compared to parent strains was also observed in glucose‐limited chemostats at low dilution rate , and could be explained due to lower accumulation of fermentative products, as discussed below. The deletion of arcA resulted in growth rate recovery, which reached 0.43 ± 0.01 h. In contrast to the creB mutant, the Y X/S of the arcA mutant was only 0.38 ± 0.00 g/g (Fig.…”

Section: Resultsmentioning

confidence: 79%

“…One of the major regulators of aerobic–anaerobic metabolism of E. coli is the ArcAB two‐component system: ArcB is a transmembrane sensor for dissolved oxygen, and aerobic respiratory control A protein (ArcA) is a cytoplasmic regulator that recognizes ArcB signals . ArcA represses the expression of genes of the TCA, like those coding for SUC dehydrogenase ( sdh ), fumarase ( fumA ), pyruvate (PYR) dehydrogenase ( pdh ) , malate dehydrogenase ( mdh ) , and malate synthase ( ace ) . ArcA also represses the expression of cyoABCDE operon, coding for the low O 2 ‐affinity cytochrome bo oxidase, and activates the expression of cydAB, coding for the high O 2 ‐affinity cytochrome bd oxidase , the pfl operon , as well as enzymes of fermentative metabolism (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…CreABCD is activated when glycolytic carbon sources are being fermented in minimal medium but not in complex media . CreABCD regulon consists of four genes: creA , which acts as an open reading frame; creD , encoding an intramembranal protein of unknown function; and creB and creC , which in resemblance to the ArcAB system, encode a cytoplasmic regulator and a sensor kinase, respectively . This system activates seven genes under microaerobic conditions , among them, those coding for the acetate kinase and phosphotransacetylase ( ackA and pta ; Fig.…”

Section: Introductionmentioning

confidence: 99%

“…), as well as transaldolase. Accordingly, it has been reported that creB mutants accumulated less organic acids and produced more biomass than its parental strain in microaerobic chemostat cultures . The second approach to develop engineered strains with better performance under microaerobic conditions is to inactivate fermentative pathways.…”

Section: Introductionmentioning

confidence: 99%

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Toward efficient microaerobic processes using engineered Escherichia coli W3110 strains

Pablos

Olivares²,

Sigala³

et al. 2016

Engineering in Life Sciences

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Operational and economic constraints in large-scale bioreactors often result in local or global microaerobic conditions, which lead to less efficient bioprocesses. Escherichia coli adapts to microaerobicity by activating fermentation pathways that accumulate acidic by-products, in detriment of growth rate (μ) and biomass yield on glucose (Y X/S ). In this study, the metabolism of E. coli was modified to better cope with microaerobicity. For that purpose, genes coding for global regulators like carbon source responsive B protein and aerobic respiratory control A protein, or for fermentative pathways were inactivated. The performance of a wild-type (W3110) and engineered E. coli strains was evaluated in batch cultures at constant low dissolved oxygen tension (3% air sat.). By combining the partial elimination of fermentation pathways and the expression of the Vitreoscilla hemoglobin (VHb), a 32% decrease on carbon waste as by-products, 24 % increase on Y X/S and 13% increase of μ were obtained. Flux balance analysis of the best strain estimated major differences in the fluxes through the pentose phosphate pathway and tricarboxylic acid cycle as consequence of VHb presence. Overall, our results show that E. coli can be genetically modified to overcome some of the disadvantages of microaerobic growth, which is potentially useful for better bioreactor scale-up and operation.

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Section: Resultsmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Toward efficient microaerobic processes using engineered Escherichia coli W3110 strains

Pablos

Olivares²,

Sigala³

et al. 2016

Engineering in Life Sciences

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show abstract

“…Since Cyo is more costly than Cyd‐I under microaerobic conditions, this would lead to a decrease in glucose transporter expression. Indeed, a decrease in GUR is indeed observed in ArcA knockout strains grown under microaerobic condition (Nikel et al , 2009).…”

Section: Resultsmentioning

confidence: 99%

Economics of membrane occupancy and respiro‐fermentation

Zhuang

Vemuri

Mahadevan

2011

Molecular Systems Biology

173

168

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Strain engineering to reduce acetate accumulation during microaerobic growth conditions in Escherichia coli

Veeravalli

Schindler

Dong³

et al. 2017

Biotechnology Progress

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Microaerobic (oxygen limited) conditions are advantageous for several industrial applications since a majority of the carbon atoms can be directed for synthesis of desired products. Oxygen limited conditions, however, can result in high levels of undesirable by-products such as acetate, which subsequently can have an impact on biomass and product yields. The molecular mechanisms involved in acetate accumulation under oxygen limited conditions are not well understood. Our results indicate that a majority of the genetic modifications known to decrease acetate under aerobic conditions results in similar or even higher acetate under oxygen limitation. Deletion of arcA, whose gene product is a global transcriptional regulator, was the only modification among those evaluated that significantly decreased acetate under both transient and prolonged oxygen limitation. Transcriptome results indicate that the arcA deletion results in an increased expression of the operon involving acs and actP (whose gene products are involved in acetate assimilation and uptake respectively) and some genes in the TCA cycle, thereby promoting increased acetate assimilation. These results provide useful cues for strain design for improved manufacturing of biopharmaceuticals under oxygen limited conditions. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:303-314, 2018.

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Metabolic flux analysis of Escherichia coli ArcA and CreB mutants reveals shared control of carbon catabolism under microaerobic conditions of growth

Cited by 8 publications

References 0 publications

Toward efficient microaerobic processes using engineered Escherichia coli W3110 strains

Toward efficient microaerobic processes using engineered Escherichia coli W3110 strains

Economics of membrane occupancy and respiro‐fermentation

Strain engineering to reduce acetate accumulation during microaerobic growth conditions in Escherichia coli

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