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Abstract：
More than a decade ago, the first genome-scale metabolic models for two of the most relevant microbes for biotechnology applications, Escherichia coli and Saccaromyces cerevisiae, were published. Shortly after followed the publication of OptKnock, the first strain design method using bilevel optimization to couple cellular growth with the production of a target product. This initiated the development of a family of strain design methods based on the concept of flux balance analysis. Another family of strain design methods, based on the concept of elementary mode analysis, has also been growing. Although the computation of elementary modes is hindered by computational complexity, recent breakthroughs have allowed applying elementary mode analysis at the genome scale. Here we review and compare strain design methods and look back at the last 10 years of in silico strain design with constraint-based models. We highlight some features of the different approaches and discuss the utilization of these methods in successful in vivo metabolic engineering applications.
摘要：
十多年前,用于生物技术应用的两种最相关微生物的第一个基因组尺度代谢模型，大肠杆菌和酿酒酵母，已发布。在OptKnock出版后不久，第一菌株设计方法使用双层优化将细胞生长与目标产品的生产耦合。这启动了基于通量平衡分析概念的应变设计方法家族的开发。另一种应变设计方法，基于基本模式分析的概念，也一直在增长。尽管基本模式的计算受到计算复杂性的阻碍，最近的突破允许在基因组规模上应用基本模式分析。在这里，我们回顾和比较应变设计方法，并回顾使用基于约束的模型进行计算机应变设计的最近10年。我们强调了不同方法的一些特征，并讨论了这些方法在成功的体内代谢工程应用中的应用。
