skip to main content
Idioma:

Computational design and engineering of an Escherichia coli strain producing the nonstandard amino acid para-aminophenylalanine

Zomorrodi, Ali R. ; Hemez, Colin ; Arranz-Gibert, Pol ; Wu, Terrence ; Isaacs, Farren J. ; Segrè, Daniel

iScience, 2022-07, Vol.25 (7), p.104562-104562, Article 104562 [Periódico revisado por pares]

United States: Elsevier Inc

Texto completo disponível

Citações Citado por
  • Título:
    Computational design and engineering of an Escherichia coli strain producing the nonstandard amino acid para-aminophenylalanine
  • Autor: Zomorrodi, Ali R. ; Hemez, Colin ; Arranz-Gibert, Pol ; Wu, Terrence ; Isaacs, Farren J. ; Segrè, Daniel
  • Assuntos: BASIC BIOLOGICAL SCIENCES ; Bioengineering ; Bioinformatics ; Metabolic engineering
  • É parte de: iScience, 2022-07, Vol.25 (7), p.104562-104562, Article 104562
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    AC02-05CH11231; HR0011-15-C-0091; EF-1935120
    National Science Foundation (NSF)
    Defense Advanced Research Projects Agency (DARPA)
    Netherlands Organization for Scientific Research (NWO)
    USDOE Office of Science (SC), Biological and Environmental Research (BER)
    These authors contributed equally
    Lead contact
  • Descrição: Introducing heterologous pathways into host cells constitutes a promising strategy for synthesizing nonstandard amino acids (nsAAs) to enable the production of proteins with expanded chemistries. However, this strategy has proven challenging, as the expression of heterologous pathways can disrupt cellular homeostasis of the host cell. Here, we sought to optimize the heterologous production of the nsAA para-aminophenylalanine (pAF) in Escherichia coli. First, we incorporated a heterologous pAF biosynthesis pathway into a genome-scale model of E. coli metabolism and computationally identified metabolic interventions in the host’s native metabolism to improve pAF production. Next, we explored different approaches of imposing these flux interventions experimentally and found that the upregulation of flux in the chorismate biosynthesis pathway through the elimination of feedback inhibition mechanisms could significantly raise pAF titers (∼20-fold) while maintaining a reasonable pAF production-growth rate trade-off. Overall, this study provides a promising strategy for the biosynthesis of nsAAs in engineered cells. [Display omitted] •Sought to optimize para-aminophenylalanine (pAF) production and growth in E. coli•Identified interventions in the host native metabolism using genome-scale models•Constructed multiple mutant strains involving gene knockouts and/or overexpressions•Flux modification in chorismate biosynthesis pathway significantly raised pAF titer Bioengineering; Metabolic engineering; Bioinformatics
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
Links
Voltar para lista de resultados
Ir para página anteriorAnterior Resultado  7 AvançarIr para próxima página

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.