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不断发展的定向进化工具包。

The developing toolkit of continuous directed evolution.

机构信息

Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.

出版信息

Nat Chem Biol. 2020 Jun;16(6):610-619. doi: 10.1038/s41589-020-0532-y. Epub 2020 May 22.

DOI:10.1038/s41589-020-0532-y
PMID:32444838
Abstract

Continuous directed evolution methods allow the key steps of evolution-gene diversification, selection, and replication-to proceed in the laboratory with minimal researcher intervention. As a result, continuous evolution can find solutions much more quickly than traditional discrete evolution methods. Continuous evolution also enables the exploration of longer and more numerous evolutionary trajectories, increasing the likelihood of accessing solutions that require many steps through sequence space and greatly facilitating the iterative refinement of selection conditions and targeted mutagenesis strategies. Here we review the historical advances that have expanded continuous evolution from its earliest days as an experimental curiosity to its present state as a powerful and surprisingly general strategy for generating tailor-made biomolecules, and discuss more recent improvements with an eye to the future.

摘要

连续定向进化方法使进化的关键步骤——基因多样化、选择和复制——可以在实验室中进行,而研究者的干预最小。因此,连续进化可以比传统的离散进化方法更快地找到解决方案。连续进化还可以探索更长、更多的进化轨迹,增加通过序列空间获取需要许多步骤的解决方案的可能性,并极大地促进选择条件和靶向诱变策略的迭代改进。在这里,我们回顾了历史上的进展,这些进展将连续进化从最初的实验好奇心扩展到了现在,使其成为一种强大而又通用的策略,用于生成定制的生物分子,并讨论了最近的改进,着眼于未来。

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