Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon, 305-701, Republic of Korea,
Adv Biochem Eng Biotechnol. 2010;120:1-19. doi: 10.1007/10_2009_57.
Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.
随机突变和选择或不考虑其对整个代谢和调控网络影响的靶向代谢工程可能会无意中导致与目标代谢物不直接相关的区域的遗传改变。这就是为什么现在开发工业菌株的策略转向基于系统生物学的靶向代谢工程的原因之一，这被称为系统代谢工程。使用系统代谢工程策略，所有代谢工程工作都在系统生物学框架内进行，从而全面综合地考虑整个代谢和调控网络。在全面考虑对整个代谢和调控网络的所有可能影响之后，才会选择有目的进行工程的目标。最终，可以构建能够产生接近理论最大值的高水平目标代谢物的菌株。在这里，我们综述了系统生物学在生物工艺工程中成功实施的策略和应用，特别关注大肠杆菌 L: -苏氨酸生产菌株的开发。
