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Increased production of L-serine in Escherichia coli through Adaptive Laboratory Evolution.
- Source :
-
Metabolic engineering [Metab Eng] 2017 Jan; Vol. 39, pp. 141-150. Date of Electronic Publication: 2016 Nov 29. - Publication Year :
- 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.<br /> (Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Biosynthetic Pathways genetics
Gene Expression Regulation, Bacterial genetics
Genetic Enhancement methods
Metabolic Networks and Pathways genetics
Serine isolation & purification
Directed Molecular Evolution methods
Escherichia coli physiology
Glucose metabolism
Metabolic Engineering methods
Serine biosynthesis
Serine genetics
Up-Regulation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7184
- Volume :
- 39
- Database :
- MEDLINE
- Journal :
- Metabolic engineering
- Publication Type :
- Academic Journal
- Accession number :
- 27908688
- Full Text :
- https://doi.org/10.1016/j.ymben.2016.11.008