Marín-Sanguino Alberto, Torres Néstor V
Departamento de Bioqímica y Biología Molecular, Facultad de Biología, Universidad de La Laguna, 38206 La Laguna, Tenerife, Islas Canarias, Spain.
Math Biosci. 2003 Aug;184(2):187-200. doi: 10.1016/s0025-5564(03)00046-4.
A new method is proposed for the optimization of biochemical systems. The method, based on the separation of the stoichiometric and kinetic aspects of the system, follows the general approach used in the previously presented indirect optimization method (IOM) developed within biochemical systems theory. It is called GMA-IOM because it makes use of the generalized mass action (GMA) as the model system representation form. The GMA representation avoids flux aggregation and thus prevents possible stoichiometric errors. The optimization of a system is used to illustrate and compare the features, advantages and shortcomings of both versions of the IOM method as a general strategy for designing improved microbial strains of biotechnological interest. Special attention has been paid to practical problems for the actual implementation of the new proposed strategy, such as the total protein content of the engineered strain or the deviation from the original steady state and its influence on cell viability.
提出了一种优化生化系统的新方法。该方法基于系统化学计量和动力学方面的分离，遵循在生化系统理论中先前提出的间接优化方法（IOM）中使用的一般方法。它被称为GMA-IOM，因为它使用广义质量作用（GMA）作为模型系统表示形式。GMA表示避免了通量聚集，从而防止了可能的化学计量误差。作为设计具有生物技术意义的改良微生物菌株的一般策略，利用系统优化来说明和比较IOM方法两个版本的特征、优点和缺点。对于新提出策略的实际实施中的实际问题，如工程菌株的总蛋白含量、与原始稳态的偏差及其对细胞活力的影响，给予了特别关注。
