作者
A Sevilla, V Bernal, R Teruel, C Bernal, M Cánovas, JL Iborra
发表日期
2006
期刊
Understanding and Exploiting Systems Biology in Biomedicine and Bioprocesses
页码范围
249
简介
System Biology allows cellular complexity analysis and the optimization of cell metabolic pathways by using cell component enumeration, structured relationship between them, mathematical representation of the metabolic networks, knowledge of the metabolic properties and comparison with experimental outputs of the cell processes involved. In this work metabolic engineering strategies and system biology principles for maximizing L (-)-carnitine production by E. coli based on the Biochemical System Theory are presented. The model integrates the metabolic and the bioreactor levels using power-law formalism. Experimental results using a high-cell density reactor were compared with optimized predictions. The model shows control points at macroscopic (reactor operation) and microscopic (molecular) levels where conversion and productivity can be increased. In accordance with the optimized solution, the next logical step to improve the L (-)-carnitine production rate will involve metabolic engineering of the E. coli strain by overexpressing the carnitine transferase, CaiB, activity and the protein carrier, CaiT, responsible for substrate and product transport in and out of the cell. By this means, it is predicted that production may be enhanced by up to three times the original value.
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A Sevilla, V Bernal, R Teruel, C Bernal, M Cánovas… - Understanding and Exploiting Systems Biology in …, 2006