Metabolic engineering for improving <scp>l</scp>-tryptophan production in <i>Escherichia coli</i>

Niu, Hao; Li, Ruirui; Liang, Quanfeng; Qi, Qingsheng; Li, Qiang; Gu, Pengfei

doi:10.1007/s10295-018-2106-5

Cited by 49 publications

(37 citation statements)

References 82 publications

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“…During the early fermentation period, the accumulation of acetate was low at a high DO level. The enhanced accumulation of acetate at a lower DO level was caused by lower TCA cycle activity and the altered transcriptional levels of genes required for glucose and acetate metabolism . The transcriptional levels of genes required for gluconeogenesis ( pck A, pps A) and the PP pathway ( pgdh D1, ybh E, and ara D) increased with higher DO level .…”

Section: Discussionmentioning

confidence: 97%

“…When low pH is maintained during the later stage of fermentation, lower concentrations of NH 4 + accumulated and the solubility of l ‐tryptophan decreased as l ‐tryptophan crystallizes, leading to diminished feedback‐inhibition of tryptophan biosynthesis. The higher transcriptional levels of genes related to tryptophan biosynthesis and lower transcriptional levels of genes for acetate formation increases the production of l ‐tryptophan . We produced higher amounts of biomass and l ‐tryptophan by maintaining pH at 7.0 (0–20 hr) and 6.5 (20–40 hr).…”

Section: Discussionmentioning

confidence: 99%

“…(e) The consumption energy and the maintenance energy were not equivalent due to too much futile energy during the nongrowth period. The metabolic network and the reaction rate equations of metabolic nodes are presented as previously described . Based on the analysis of metabolic flux balance and the stoichiometry model, combined with the strain being in stationary phase during the end of the fermentation period, the metabolic flux distribution of tryptophan biosynthesis by E. coli D mtr / pta ‐Y was calculated using MATLAB (MathWorks, Natick) …”

Section: Methodsmentioning

confidence: 99%

“…For humans and other animals, l ‐tryptophan is an essential aromatic amino acid. l ‐tryptophan is used widely in food additives, animal feed, and pharmaceuticals . Due to its commercial importance, there is increasing interest in improving the production of l ‐tryptophan .…”

Section: Introductionmentioning

confidence: 99%

“…L-tryptophan is used widely in food additives, animal feed, and pharmaceuticals. 1,2 Due to its commercial importance, there is increasing interest in improving the production of L-tryptophan. 3 L-tryptophan produced by direct fermentation can be increased by genetic modification of strains and optimization of culture parameters.…”

Section: Introductionmentioning

confidence: 99%

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Application of fermentation process control to increase l‐tryptophan production in Escherichia coli

Zhao

Fang

Jing

et al. 2019

Biotechnology Progress

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In this study, process engineering and process control were applied to increase the production of l‐tryptophan using Escherichia coli Dmtr/pta‐Y. Different dissolved oxygen (DO) and pH control strategies were applied in l‐tryptophan production. DO and pH were maintained at [20% (0–20 hr); 30% (20–40 hr)] and [7.0 (0–20 hr), 6.5 (20–40 hr)], respectively, which increased l‐tryptophan production, glucose conversion percentage [g (l‐tryptophan)/g (glucose)], and transcription levels of key genes for tryptophan biosynthesis and tryptophan biosynthesis flux, and decreased the accumulation of acetate and transcription levels of genes related to acetate synthesis and acetate synthesis flux. Using E. coli Dmtr/pta‐Y with optimized DO [20% (0–20 hr); 30% (20–40 hr)] and pH [7.0 (0–20 hr), 6.5 (20–40 hr)] values, the highest l‐tryptophan production (52.57 g/L) and glucose conversion percentage (20.15%) were obtained. The l‐tryptophan production was increased by 26.58%, the glucose conversion percentage was increased by 22.64%, and the flux of tryptophan biosynthesis was increased to 21.5% compared with different conditions for DO [50% (0–20 hr), 20% (20–40 hr)] and pH [7.0].

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Application of fermentation process control to increase l‐tryptophan production in Escherichia coli

Zhao

Fang

Jing

et al. 2019

Biotechnology Progress

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Enhancing tryptophan production by balancing precursors in Escherichia coli

Guo

Ding

Liu

et al. 2021

Biotech & Bioengineering

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Tryptophan, an essential aromatic amino acid, is widely used in animal feed, food additives, and pharmaceuticals. Although sustainable and environmentally friendly, microbial tryptophan production from renewable feedstocks is limited by low biosynthesis and transport rates. Here, an Escherichia coli strain capable of efficient tryptophan production was generated by improving and balancing the supply of precursors and by engineering membrane transporters. Tryptophan biosynthesis was increased by eliminating negative regulatory factors, blocking competing pathways, and preventing tryptophan degradation. Promoter engineering balanced the supply of the precursors erythrose-4-phosphate and phosphoenolpyruvate, as well as the availability of serine. Finally, the engineering of tryptophan transporters prevented feedback inhibition and growth toxicity. Fed-batch fermentation of the final strain (TRP12) in a 5 L bioreactor produced 52.1 g•L −1 of tryptophan, with a yield of 0.171 g•g −1 glucose and productivity of 1.45 g•L −1 •h −1 . The metabolic engineering strategy described here paves the way for high-performance microbial cell factories aimed at the production of tryptophan as well as other valuable chemicals.

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Biotransformation Of l‐Tryptophan To Produce Arcyriaflavin A With Pseudomonas putida KT2440

Bitzenhofer,

Classen,

Jaeger

et al. 2023

ChemBioChem

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Natural products such as indolocarbazoles are a valuable source of highly bioactive compounds with numerous potential applications in the pharmaceutical industry. Arcyriaflavin A, isolated from marine invertebrates and slime molds, is one representative of this group and acts as a cyclin D1‐cyclin‐dependent kinase 4 inhibitor. To date, access to this compound has mostly relied on multi‐step total synthesis. In this study, biosynthetic access to arcyriaflavin A was explored using recombinant Pseudomonas putida KT2440 based on a previously generated producer strain. We used a Design of Experiment approach to analyze four key parameters, which led to the optimization of the bioprocess. By engineering the formation of outer membrane vesicles and using an adsorbent in the culture broth, we succeeded to increase the yield of arcyriaflavin A in the cell‐free supernatant, resulting in a nearly eight‐fold increase in the overall production titers. Finally, we managed to scale up the bioprocess leading to a final yield of 4.7 mg arcyriaflavin A product isolated from 1 L of bacterial culture. Thus, this study showcases an integrative approach to improve a biotransformation and moreover also provides starting points for further optimization of indolocarbazole production in P. putida.

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Metabolic engineering for improving l-tryptophan production in Escherichia coli

Cited by 49 publications

References 82 publications

Application of fermentation process control to increase l‐tryptophan production in Escherichia coli

Application of fermentation process control to increase l‐tryptophan production in Escherichia coli

Enhancing tryptophan production by balancing precursors in Escherichia coli

Biotransformation Of l‐Tryptophan To Produce Arcyriaflavin A With Pseudomonas putida KT2440

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