Genetically switched d-lactate production in Escherichia coli

Zhou, Li; Niu, Dong Xiao; Tian, Kangming; Chen, Xiang‐Zhong; Prior, Bernard A.; Shen, Wei; Shi, Guiyang; Singh, Surendra; Wang, Zhengxiang

doi:10.1016/j.ymben.2012.05.004

Cited by 78 publications

(59 citation statements)

References 37 publications

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“…The optical purity of the d-lactate produced under these circumstances was >99.9 %. These values are similar to those obtained when using metabolically engineered E. coli B0013-070B (122.8 g/L of d-lactate within 28 h, with a yield of 1.69 mol/mol glucose [90] [ Table 1]), as strain LPglc279/pCRB215 produced 1,394 mM (125.6 g/L) d-lactate within 32 h.…”

Section: Introductionsupporting

confidence: 80%

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Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources

Tsuge

Hasunuma

Kondo

2015

Journal of Industrial Microbiology and Biotechnology

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Recent increasing attention to environmental issues and the shortage of oil resources have spurred political and industrial interest in the development of environmental friendly and cost-effective processes for the production of bio-based chemicals from renewable resources. Thus, microbial production of commercially important chemicals is viewed as a desirable way to replace current petrochemical production. Corynebacterium glutamicum, a Gram-positive soil bacterium, is one of the most important industrial microorganisms as a platform for the production of various amino acids. Recent research has explored the use of C. glutamicum as a potential cell factory for producing organic acids such as lactate and succinate, both of which are commercially important bulk chemicals. Here, we summarize current understanding in this field and recent metabolic engineering efforts to develop C. glutamicum strains that efficiently produce L- and D-lactate, and succinate from renewable resources.

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Section: Introductionsupporting

confidence: 80%

“…Moreover, the presence of d-lactate is essential for the growth of some lactic acid bacteria, which spoils the optical purity [15]. Other microorganisms, such as metabolically engineered Escherichia coli, have been developed for large-scale and cost-effective l-and d-lactate production in minimal medium [47,90].…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources

Tsuge

Hasunuma

Kondo

2015

Journal of Industrial Microbiology and Biotechnology

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“…The advantage of this control system is that it can be regulated simply by changing the temperature and does not require an expensive inducer, a pre‐condition for industrial applications. The dynamic activation of the lactate production pathway in an oxygen‐limited phase at 42°C with this genetic switch successfully increased d ‐lactate production by E. coli (Zhou et al, 2012). Although it has been shown that the Lambda promoters can be used in the opposite direction to switch genes off (Cho et al, 2012), they have not been used so far in this way to improve cell factory performance.…”

Section: Resultsmentioning

confidence: 99%

Temperature‐dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli

Harder

Bettenbrock

Klamt

2017

Biotech & Bioengineering

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Based on the recently constructed Escherichia coli itaconic acid production strain ita23, we aimed to improve the productivity by applying a two‐stage process strategy with decoupled production of biomass and itaconic acid. We constructed a strain ita32 (MG1655 ΔaceA Δpta ΔpykF ΔpykA pCadCs), which, in contrast to ita23, has an active tricarboxylic acid (TCA) cycle and a fast growth rate of 0.52 hr−1 at 37°C, thus representing an ideal phenotype for the first stage, the growth phase. Subsequently we implemented a synthetic genetic control allowing the downregulation of the TCA cycle and thus the switch from growth to itaconic acid production in the second stage. The promoter of the isocitrate dehydrogenase was replaced by the Lambda promoter (p R) and its expression was controlled by the temperature‐sensitive repressor CI857 which is active at lower temperatures (30°C). With glucose as substrate, the respective strain ita36A grew with a fast growth rate at 37°C and switched to production of itaconic acid at 28°C. To study the impact of the process strategy on productivity, we performed one‐stage and two‐stage bioreactor cultivations. The two‐stage process enabled fast formation of biomass resulting in improved peak productivity of 0.86 g/L/hr (+48%) and volumetric productivity of 0.39 g/L/hr (+22%) in comparison to the one‐stage process. With our dynamic production strain, we also resolved the glutamate auxotrophy of ita23 and increased the itaconic acid titer to 47 g/L. The temperature‐dependent activation of gene expression by the Lambda promoters (p R/p L) has been frequently used to improve protein or, in a few cases, metabolite production in two‐stage processes. Here we demonstrate that the system can be as well used in the opposite direction to selectively knock‐down an essential gene (icd) in E. coli to design a two‐stage process for improved volumetric productivity. The control by temperature avoids expensive inducers and has the potential to be generally used to improve cell factory performance.

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“…Bio-based chemicals can be produced with engineered E. coli at low production cost because of its rapid doubling time and growth rate, ease of high-cell-density fermentation, and the availability of excellent genetic tools for strain improvement. Zhou et al [38] have developed an engineered E. coli strain (B0013-070B) to exhibit high overall volumetric productivity and the oxygen-limited productivity of 4.32 and 6.73 g/L/h, respectively. Moreover, the D-lactate productivity was 122.8 g/L, with an increased oxygen-limited productivity of 0.89 g/g/h, revealing the effectiveness of using a genetic switch to regulate cell growth and the production of a metabolic compound.…”

Section: Development Of Innovative Bio-conversion and Separations Tecmentioning

confidence: 99%

Development of Low-Carbon-Driven Bio-product Technology Using Lignocellulosic Substrates from Agriculture: Challenges and Perspectives

Pan

Lin

Snyder

et al. 2015

Curr Sustainable Renewable Energy Rep

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Green biotechnology related to biomass conversion for production of bio-based chemicals has drawn considerable attention because of the increasing costs of fossil fuels and their adverse effects on climate change, environmental pollution, and human health. In this study, the recent promises and issues of low-carbon-driven bio-product technology development using lignocellulosic substrates from agriculture were critically reviewed. First, the challenges in bio-based chemical production were addressed from the aspect of technology. After that, the lignocellulose feedstock and their buildingblock chemicals used in the literature were summarized. In addition, novel pretreatment, bio-conversion, and separations technologies for cleaner production of bio-based products were comprehensively reviewed. It suggests that the main challenge to deploying bio-based chemical technologies into commercialization is the high cost of product recovery from the bioreactor due to the relatively low product titers caused by the product inhibition and/or pH in conventional fermentation.

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Genetically switched d-lactate production in Escherichia coli

Cited by 78 publications

References 37 publications

Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources

Recent advances in the metabolic engineering of Corynebacterium glutamicum for the production of lactate and succinate from renewable resources

Temperature‐dependent dynamic control of the TCA cycle increases volumetric productivity of itaconic acid production by Escherichia coli

Development of Low-Carbon-Driven Bio-product Technology Using Lignocellulosic Substrates from Agriculture: Challenges and Perspectives

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