Optimising the function of a protein of length N amino acids by directed evolution involves navigating a ‘search space’ of possible sequences of some 20N. Optimising the expression levels of P proteins that materially affect host performance, each of which might also take 20 (logarithmically spaced) values, implies a similar search space of 20P. In this combinatorial sense, then, the problems of directed protein evolution and of host engineering are broadly equivalent. In practice, however, they have different means for avoiding the inevitable difficulties of implementation. The spare capacity exhibited in metabolic networks implies that host engineering may admit substantial increases in flux to targets of interest. Thus, we rehearse the relevant issues for those wishing to understand and exploit those modern genome-wide host engineering tools and thinking that have been designed and developed to optimise fluxes towards desirable products in biotechnological processes, with a focus on microbial systems. The aim throughput is ‘making such biology predictable’. Strategies have been aimed at both transcription and translation, especially for regulatory processes that can affect multiple targets. However, because there is a limit on how much protein a cell can produce, increasing kcat in selected targets may be a better strategy than increasing protein expression levels for optimal host engineering.

中文翻译：

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用于生物技术中代谢通量优化的智能宿主工程

通过定向进化优化长度为 N 个氨基酸的蛋白质的功能涉及在大约 20N 的可能序列的“搜索空间”中导航。优化对宿主性能产生重大影响的 P 蛋白的表达水平，每个 P 蛋白也可能取 20 个（对数间隔）值，这意味着 20P 的类似搜索空间。那么，在这种组合意义上，定向蛋白质进化和宿主工程的问题是大致等价的。然而，在实践中，它们有不同的方法来避免不可避免的实施困难。代谢网络中表现出的备用容量意味着宿主工程可能会允许目标目标的通量大幅增加。因此，我们为那些希望了解和利用现代全基因组宿主工程工具和思想的人排练相关问题，这些工具和思想是为优化生物技术过程中所需产品的通量而设计和开发的，重点是微生物系统。目标吞吐量是“使这种生物学可预测”。策略一直针对转录和翻译，特别是针对可能影响多个目标的监管过程。然而，由于细胞可以产生多少蛋白质是有限度的，因此增加选定目标中的 kcat 可能是比增加蛋白质表达水平以获得最佳宿主工程更好的策略。目标吞吐量是“使这种生物学可预测”。策略一直针对转录和翻译，特别是针对可能影响多个目标的监管过程。然而，由于细胞可以产生多少蛋白质是有限度的，因此增加选定目标中的 kcat 可能是比增加蛋白质表达水平以获得最佳宿主工程更好的策略。目标吞吐量是“使这种生物学可预测”。策略一直针对转录和翻译，特别是针对可能影响多个目标的监管过程。然而，由于细胞可以产生多少蛋白质是有限度的，因此增加选定目标中的 kcat 可能是比增加蛋白质表达水平以获得最佳宿主工程更好的策略。