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Improving lysine production through construction of an Escherichia coli enzyme‐constrained model
Author(s) -
Ye Chao,
Luo Qiuling,
Guo Liang,
Gao Cong,
Xu Nan,
Zhang Li,
Liu Liming,
Chen Xiulai
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27485
Subject(s) - lysine , escherichia coli , enzyme , biochemistry , enzyme kinetics , metabolism , yield (engineering) , titer , metabolic engineering , chemistry , biology , amino acid , active site , materials science , antibody , immunology , metallurgy , gene
Microbial cell factories are widely used for the production of high‐value chemicals. However, maximizing production titers is made difficult by the complicated regulatory mechanisms of these cell platforms. Here, k cat values were incorporated to construct an Escherichia coli enzyme‐constrained model. The resulting ec_ i ML1515 model showed that the protein demand and protein synthesis rate were the key factors affecting lysine production. By optimizing the expression of the 20 top‐demanded proteins, lysine titers reached 95.7 ± 0.7 g/L, with a 0.45 g/g glucose yield. Moreover, adjusting NH 4 + and dissolved oxygen levels to regulate the synthesis rate of energy metabolism‐related proteins caused lysine titers and glucose yields to increase to 193.6 ± 1.8 g/L and 0.74 g/g, respectively. The ec_ i ML1515 model provides insight into how enzymes required for the biosynthesis of certain products are distributed between and within metabolic pathways. This information can be used to accurately predict and rationally design lysine production.