From the first drop to the first truckload: commercialization of microbial processes for renewable chemicals

Dien, Stephen Van

doi:10.1016/j.copbio.2013.03.002

Cited by 163 publications

(111 citation statements)

References 51 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…Compared to our production strain ita23 the titer was improved by 46% and the peak volumetric productivity by 91%. In addition we could resolve the glutamate auxotrophy and the reached titer of 46.9 g/L is close to the recommended value of 50 g/L for commercialization of bioprocesses (Van Dien, 2013). This shows the further advantage of two‐stage processes: growth‐essential genes can be knocked‐down in the production phase without further medium supplementation.…”

Section: Resultssupporting

confidence: 76%

“…To become competitive with traditional chemical processes, bio‐based processes for bulk chemicals should have a minimum yield of 80% of the theoretical yield, a titer of 50 g/L and a volumetric productivity of around 3 g/L/hr (Van Dien, 2013; Werpy & Petersen, 2004). Improvements of yield and titer by genetic engineering or process optimization have been realized for a wide range of products including amino acids, organic acids, or biofuels, however, the volumetric productivity remained low in most cases (Becker & Wittmann, 2015).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Harder

Bettenbrock

Klamt

2017

Biotech & Bioengineering

103

View full text Add to dashboard Cite

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.

show abstract

Section: Resultssupporting

confidence: 76%

Section: Introductionmentioning

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

103

View full text Add to dashboard Cite

show abstract

“…426 Higher values were indeed found, except for citric acid and itaconic acid. These traditional products require aerobic fermentations, but the achievable productivities may easily be limited by oxygen transfer rates in the used fungal pellets.…”

Section: Feasible Productivitiesmentioning

confidence: 86%

Transformation of Biomass into Commodity Chemicals Using Enzymes or Cells

2013

View full text Add to dashboard Cite

“…Thus, we propose that systematic highresolution characterization of the steady-state growth space of cells using changestats should not only be used for fundamental studies of metabolism, but also incorporated into the systems microbiology-based metabolic engineering pipeline (Fig. 3) (Van Dien, 2013). Comprehensive systems microbiology through coupling advanced continuous cultivation methods, -omics technologies and metabolic modelling could lead to more efficient cell designs.…”

Section: Resultsmentioning

confidence: 99%

Advanced continuous cultivation methods for systems microbiology

2015

View full text Add to dashboard Cite

Increasing the throughput of systems biology-based experimental characterization of in silicodesigned strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady stategrowth space analysis (GSA) -can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories.

show abstract

From the first drop to the first truckload: commercialization of microbial processes for renewable chemicals

Cited by 163 publications

References 51 publications

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

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

Transformation of Biomass into Commodity Chemicals Using Enzymes or Cells

Advanced continuous cultivation methods for systems microbiology

Contact Info

Product

Resources

About