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Increased production of L-serine in Escherichia coli through Adaptive Laboratory Evolution
- Source :
- Mundhada, H, Seoane, J M, Schneider, K, Christensen, H B, Koza, A, Herrgard, M, Feist, A & Nielsen, A T 2017, ' Increased production of L-serine in Escherichia coli through Adaptive Laboratory Evolution ', Metabolic Engineering, vol. 39, pp. 141–150 . https://doi.org/10.1016/j.ymben.2016.11.008
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- L-serine is a promising building block biochemical with a high theoretical production yield from glucose. Toxicity of L-serine is however prohibitive for high-titer production in E. coli. Here, E. coli lacking L-serine degradation pathways was evolved for improved tolerance by gradually increasing L-serine concentration from 3 to 100g/L using adaptive laboratory evolution (ALE). Genome sequencing of isolated clones revealed multiplication of genetic regions, as well as mutations in thrA, thereby showing a potential mechanism of serine inhibition. Additional mutations were evaluated by MAGE combined with amplicon sequencing, revealing role of rho, lrp, pykF, eno, and rpoB on tolerance and fitness in minimal medium. Production using the tolerant strains resulted in 37g/L of L-serine with a 24% mass yield. The resulting titer is similar to the highest production reported for any organism thereby highlighting the potential of ALE for industrial biotechnology.
- Subjects :
- 0301 basic medicine
030106 microbiology
Bioengineering
Biology
medicine.disease_cause
Applied Microbiology and Biotechnology
DNA sequencing
Microbiology
Serine
03 medical and health sciences
Escherichia coli
medicine
Genetics
Gene Expression Regulation, Bacterial
rpoB
Biosynthetic Pathways
Up-Regulation
Titer
Genetic Enhancement
Glucose
030104 developmental biology
Metabolic Engineering
Yield (chemistry)
Toxicity
Fermentation
Directed Molecular Evolution
Metabolic Networks and Pathways
Biotechnology
Subjects
Details
- ISSN :
- 10967176
- Volume :
- 39
- Database :
- OpenAIRE
- Journal :
- Metabolic Engineering
- Accession number :
- edsair.doi.dedup.....9a2d9349a682009ebb07ef15ba5232de