Quantification of proteomic and metabolic burdens predicts growth retardation and overflow metabolism in recombinant Escherichia coli.

Abstract:

:Escherichia coli has been the host organism most frequently investigated for efficient recombinant protein production. However, the production of a foreign protein in recombinant E. coli often leads to growth deterioration and elevated secretion of acetic acid. Such observed phenomena have been widely linked with cell stress responses and metabolic burdens originated particularly from the increased energy demand. In this study, flux balance analysis and dynamic flux balance analysis were applied to investigate the observed growth physiology of recombinant E. coli, incorporating the proteome allocation theory and an adjustable maintenance energy level (ATPM) to capture the proteomic and energetic burdens introduced by recombinant protein synthesis. Model predictions of biomass growth, substrate consumption, acetate excretion, and protein production with two different strains were in good agreement with the experimental data, indicating that the constraint on the available proteomic resource and the change in ATPM might be important contributors governing the growth physiology of recombinant strains. The modeling framework developed in this work, currently with several limitations to overcome, offers a starting point for the development of a practical, model-based tool to guide metabolic engineering decisions for boosting recombinant protein production.

journal_name

Biotechnol Bioeng

authors

Zeng H,Yang A

doi

10.1002/bit.26943

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

1484-1495

issue

6

eissn

0006-3592

issn

1097-0290

journal_volume

116

pub_type

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