基于代谢网络预测菌种基因改造靶点方法的研究进展

Predicting genetic modification targets based on metabolic network analysis–a review

摘要:

高产特定产品的人工细胞工厂的构建需要对野生菌株进行大量的基因工程改造，近年来随着大量基因组尺度代谢网络模型的构建，人们提出了多种基于代谢网络分析预测基因改造靶点以使某一目标化合物合成最优的方法。这些方法利用基因组尺度代谢网络模型中的反应计量关系约束和反应不可逆性约束等，通过约束优化的方法预测可使产物合成最大化的改造靶点，避免了传统的通过相关途径的直观分析确定靶点的方法的局限性和主观性，为细胞工厂的理性设计提供了新的思路。以下结合作者的实际研究经验，对这些菌种优化方法的原理、优缺点及适用性等进行详细介绍，并讨论了目前存在的主要问题和未来的研究方向，为人们针对不同目标产品选择合适的方法及预测结果的可靠性评估提供了指导。

Abstract:

Construction of artificial cell factory to produce specific compounds of interest needs wild strain to be genetically engineered. In recent years, with the reconstruction of many genome-scale metabolic networks, a number of methods have been proposed based on metabolic network analysis for predicting genetic modification targets that lead to overproduction of compounds of interest. These approaches use constraints of stoichiometry and reaction reversibility in genome-scale models of metabolism and adopt different mathematical algorithms to predict modification targets, and thus can discover new targets that are difficult to find through traditional intuitive methods. In this review, we introduce the principle, merit, demerit and application of various strain optimization methods in detail. The main problems in existing methods and perspectives on this emerging research field are also discussed, aiming to provide guidance to choose the appropriate methods according to different types of products and the reliability of the predicted results.