Changes in substrate availability in Escherichia coli lead to rapid metabolite, flux and growth rate responses
Metabolic Engineering, cilt.16, sa.1, ss.115-129, 2013 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 16 Sayı: 1
- Basım Tarihi: 2013
- Doi Numarası: 10.1016/j.ymben.2013.01.004
- Dergi Adı: Metabolic Engineering
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.115-129
- Anahtar Kelimeler: Growth rate, In vivo kinetics, Intracellular metabolites, Metabolic flux analysis, Stimulus response experiments
- Boğaziçi Üniversitesi Adresli: Hayır
Özet
The interactions between the intracellular metabolome, fluxome and growth rate of Escherichia coli after sudden glycolytic/gluconeogenic substrate shifts are studied based on pulses of different substrates to an aerobic glucose-limited steady-state (dilution rate=0.1h-1). After each added glycolytic (glucose) and gluconeogenic (pyruvate and succinate) substrate pulse, no by-products were secreted and a pseudo steady state in flux and metabolites was achieved in about 30-40s. In the pulse experiments a large oxygen uptake capacity of the cells was observed. The in vivo dynamic responses showed massive reorganization and flexibility (1/100-14-fold change) of extra/intracellular metabolic fluxes, matching with large changes in the concentrations of intracellular metabolites, including reversal of reaction rate for pseudo/near equilibrium reactions. The coupling of metabolome and fluxome could be described by Q-linear kinetics. Remarkably, the three different substrate pulses resulted in a very similar increase in growth rate (0.13-0.3h-1). Data analysis showed that there must exist as yet unknown mechanisms which couple the protein synthesis rate to changes in central metabolites. © 2013 Elsevier Inc.