Kinetic evaluation of products inhibition to succinic acid producers Escherichia coli NZN111, AFP111, BL21, and Actinobacillus succinogenes 130ZT

Li, Qiang; Wang, Dan; Wu, Yong; Yang, Maohua; Li, Wangliang; Xing, Jianmin; Su, Zhiguo

doi:10.1007/s12275-010-9262-2

Cited by 38 publications

(15 citation statements)

References 28 publications

(28 reference statements)

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“…It was recently reported that E. coli strains NZN111, AFP111, and BL21 can tolerate up to 680 mM of succinate [32], a concentration similar to the predicted titer of the fast-growing strains, but much higher than the predicted titer of the slow-growing strains (Figure 6D). As such, it seems that this inhibitory effect will significantly reduce the consolidated performance of the slow-growing, high yield strains in some situations, making such strains less valuable.…”

Section: Resultssupporting

confidence: 57%

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Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and productivity. DySScO strategy for strain design

et al. 2013

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BackgroundIn recent years, constraint-based metabolic models have emerged as an important tool for metabolic engineering; a number of computational algorithms have been developed for identifying metabolic engineering strategies where the production of the desired chemical is coupled with the growth of the organism. A caveat of the existing algorithms is that they do not take the bioprocess into consideration; as a result, while the product yield can be optimized using these algorithms, the product titer and productivity cannot be optimized. In order to address this issue, we developed the Dynamic Strain Scanning Optimization (DySScO) strategy, which integrates the Dynamic Flux Balance Analysis (dFBA) method with existing strain algorithms.ResultsIn order to demonstrate the effective of the DySScO strategy, we applied this strategy to the design of Escherichia coli strains targeted for succinate and 1,4-butanediol production respectively. We evaluated consequences of the tradeoff between growth yield and product yield with respect to titer and productivity, and showed that the DySScO strategy is capable of producing strains that balance the product yield, titer, and productivity. In addition, we evaluated the economic viability of the designed strain, and showed that the economic performance of a strain can be strongly affected by the price difference between the product and the feedstock.ConclusionOur study demonstrated that the DySScO strategy is a useful computational tool for designing microbial strains with balanced yield, titer, and productivity, and has potential applications in evaluating the economic performance of the design strains.

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Section: Resultssupporting

confidence: 57%

“…Based on the work of Li et al (2010) on four E. coli strains [32], we estimated S succ,* to be 80g/L or 678mM of succinate. k is a fitting parameter that determines that shape of the inhibition curve, which we assumed to be at 1.5.…”

Section: Methodsmentioning

confidence: 99%

Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and productivity. DySScO strategy for strain design

et al. 2013

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“…Most of the data in Figure 1 fall within the blue ‘data cloud’ and drastic growth inhibition is reflected by lower growth rates between 8 and 14 g.L −1 of SA. Surprisingly, the SA titre in Figure 1 does not correspond to the terminal SA titre when succinate is externally added prior to the fermentation [22,28]. In both these studies, growth was observed above SA titres of 30 g.L −1 indicating a difference between the influence of external and produced succinate on A. succinogenes .…”

Section: Introductionmentioning

confidence: 99%

Succinic acid production with Actinobacillus succinogenes: rate and yield analysis of chemostat and biofilm cultures

Brink

Nicol

2014

Microb Cell Fact

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BackgroundSuccinic acid is well established as bio-based platform chemical with production quantities expecting to increase exponentially within the next decade. Actinobacillus succinogenes is by far the most studied wild organism for producing succinic acid and is known for high yield and titre during production on various sugars in batch culture. At low shear conditions continuous fermentation with A. succinogenes results in biofilm formation. In this study, a novel shear controlled fermenter was developed that enabled: 1) chemostat operation where self-immobilisation was opposed by high shear rates and, 2) in-situ removal of biofilm by increasing shear rates and subsequent analysis thereof.ResultsThe volumetric productivity of the biofilm fermentations were an order of magnitude more than the chemostat runs. In addition the biofilm runs obtained substantially higher yields. Succinic acid to acetic acid ratios for chemostat runs were 1.28±0.2 g.g-1, while the ratios for biofilm runs started at 2.4 g.g-1 and increased up to 3.3 g.g-1 as glucose consumption increased. This corresponded to an overall yield on glucose of 0.48±0.05 g.g-1 for chemostat runs, while the yields varied between 0.63 g.g-1 and 0.74 g.g-1 for biofilm runs. Specific growth rates (μ) were shown to be severely inhibited by the formation of organic acids, with μ only 12% of μmax at a succinic acid titre of 7 g.L-1. Maintenance production of succinic acid was shown to be dominant for the biofilm runs with cell based production rates (extracellular polymeric substance removed) decreasing as SA titre increases.ConclusionsThe novel fermenter allowed for an in-depth bioreaction analysis of A. succinogenes. Biofilm cells achieve higher SA yields than suspended cells and allow for operation at higher succinic acid titre. Both growth and maintenance rates were shown to drastically decrease with succinic acid titre. The A. succinogenes biofilm process has vast potential, where self-induced high cell densities result in higher succinic acid productivity and yield.

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“…10,11 AFP111 was a spontaneous glucose transporter (ptsG) mutation of NZN111, which produced succinate from glucose with a yield of nearly 0.9 mol mol −1 glucose containing only native genes. 12,13 Strain HL27659k was engineered by mutating succinate dehydrogenase (sdhAB), phosphotransacetylase (pta), acetate kinase (ackA), pyruvate oxidase (poxB), ptsG, and the isocitrate lyase repressor (iclR).…”

Section: Introductionmentioning

confidence: 99%

High cell density fermentation via a metabolically engineered Escherichia coli for the enhanced production of succinic acid

Wang

Song

et al. 2010

J of Chemical Tech & Biotech

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BACKGROUND: Succinic acid is a valuable four-carbon organic chemical with applications in many fields. It was found that cell mass was an important factor in succinic acid production by metabolically engineered Escherichia coli strains. In this work, high cell density fermentation was investigated for succinic acid production by a metabolically engineered strain SD121 with ldhA, pflB, ptsG mutation and heterogenous cyanobacterial ppc overexpression.

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Kinetic evaluation of products inhibition to succinic acid producers Escherichia coli NZN111, AFP111, BL21, and Actinobacillus succinogenes 130ZT

Cited by 38 publications

References 28 publications

Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and productivity. DySScO strategy for strain design

Dynamic strain scanning optimization: an efficient strain design strategy for balanced yield, titer, and productivity. DySScO strategy for strain design

Succinic acid production with Actinobacillus succinogenes: rate and yield analysis of chemostat and biofilm cultures

High cell density fermentation via a metabolically engineered Escherichia coli for the enhanced production of succinic acid

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