Increased production of L-serine in Escherichia coli through Adaptive Laboratory Evolution.

TitleIncreased production of L-serine in Escherichia coli through Adaptive Laboratory Evolution.
Publication TypeJournal Article
Year of Publication2016
AuthorsMundhada H, Seoane JM, Schneider K, Koza A, Christensen HB, Klein T, Phaneuf PV, Herrgard M, Feist AM, Nielsen AT
JournalMetab Eng
Volume39
Pagination141-150
PubMed Date11/2016
ISSN1096-7184
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.

Alternate JournalMetab. Eng.
PubMed ID27908688
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