Retrosynthetic design of heterologous pathways.
Retrosynthetic design of heterologous pathways.
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DOI：
10.1007/978-1-62703-299-5_9
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发表时间：
2013-01-01
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影响因子：
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通讯作者：
Faulon, Jean-Loup
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文献类型：
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作者：
Carbonell, Pablo;Planson, Anne-Gaelle;Faulon, Jean-Loup
代谢工程和合成生物学的工具协同使用，以开发高性能的细胞工厂。然而，成功的应用程序的数量有限，由于有效地探索代谢空间的候选异源途径的发现的复杂性。为了应对这一挑战，逆合成生物学提供了一个综合框架，正式和合理化的问题，进口生物合成途径到底盘有机体使用的方法在接口从自下而上和自上而下的战略。在这里，我们一步一步地描述了在底盘生物体中设计异源生物合成途径的逆转录合成框架的实施过程。该方法由以下步骤组成：选择底盘和目标，选择底盘的计算机模型，定义代谢空间，途径枚举，基因选择，估计产量，途径代谢物的毒性预测，定义目标函数以选择最佳途径候选物，以及途径实施和验证。
Tools from metabolic engineering and synthetic biology are synergistically used in order to develop high-performance cell factories. However, the number of successful applications has been limited due to the complexity of exploring efficiently the metabolic space for the discovery of candidate heterologous pathways. To address this challenge, retrosynthetic biology provides an integrated framework to formalize and rationalize the problem of importing biosynthetic pathways into a chassis organism using methods at the interface from bottom-up and top-down strategies. Here, we describe step by step the process of implementing a retrosynthetic framework for the design of heterologous biosynthetic pathways in a chassis organism. The method consists of the following steps: choosing the chassis and the target, selection of an in silico model for the chassis, definition of the metabolic space, pathway enumeration, gene selection, estimation of yields, toxicity prediction of pathway metabolites, definition of an objective function to select the best pathway candidates, and pathway implementation and verification.