美国科学家在《自然》杂志上撰文指出，他们利用噬菌体，在实验室中让生物分子的进化速度提高了100倍。新研究有望让制药业使用实验室培育出来的蛋白质、核酸和其他成分按需制药。
噬菌体辅助持续进化（PACE）
该研究的领导者、哈佛大学化学和生化教授戴维·刘说，大多数现代药物都由有机小分子制成，但某些情况下，蛋白质或核酸等生物大分子可能更适合用来制药。但这种生物大分子如何快速地制造一直是一大难题，新研究提供了一种新的解决办法。
科学家表示，虽然生物分子也会自然进化，但整个进化过程耗时很长，最终结果也无法控制。因此，几十年来，科学家一直使用实验室进化（直接进化）来生产具有特定性能的生物分子，但实验室进化的速率通常为每几天一轮，而且，在此期间，科学家或技术人员需要定期对样本进行操作。
而戴维·刘和同事研究出来的最新方法——噬菌体辅助持续进化（PACE）通过让生物分子的实验室进化和一种噬菌体的生命周期结合在一起，让蛋白质在每24小时内进化60轮。
PACE的效率是传统实验室进化方法的100倍左右，整个实验过程也无需人为干预，大大节省了科学家的劳动成本。除此之外，新方法使用的材料也很容易获得，另外，也可通过设计，拦住某些不需要的“骗子”分子。
科学家表示，该噬菌体的生命周期仅为10分钟，是已知噬菌体中生命周期最短的。PACE系统使用大肠杆菌的宿主细胞作为制造噬菌体细胞的工厂，使用噬菌体的基因编码让生物分子繁殖，生成所需要的蛋白质。
科学家在《自然》杂志上写道：“实验室进化已制造出很多具有特定性能的生物分子，但一轮变异、基因表达、筛选或选择、复制过程一般耗时几天甚至更长时间，而且需要人为干预。既然进化成功与否主要取决于最终进化出的轮数，因此，一种让实验室进化更快速进行的方法能显著增强其效率。”（生物谷Bioon.com）
生物谷推荐原文出处：
Nature doi:10.1038/nature09929
A system for the continuous directed evolution of biomolecules
Kevin M. Esvelt,1 Jacob C. Carlson2 & David R. Liu2, 3
Laboratory evolution has generated many biomolecules with desired properties, but a single round of mutation, gene expression, screening or selection, and replication typically requires days or longer with frequent human intervention1. Because evolutionary success is dependent on the total number of rounds performed2, a means of performing laboratory evolution continuously and rapidly could dramatically enhance its effectiveness3. Although researchers have accelerated individual steps in the evolutionary cycle4, 5, 6, 7, 8, 9, the only previous example of continuous directed evolution was the landmark study of Wright and Joyce10, who continuously evolved RNA ligase ribozymes with an in vitro replication cycle that unfortunately cannot be easily adapted to other biomolecules. Here we describe a system that enables the continuous directed evolution of gene-encoded molecules that can be linked to protein production in Escherichia coli. During phage-assisted continuous evolution (PACE), evolving genes are transferred from host cell to host cell through a modified bacteriophage life cycle in a manner that is dependent on the activity of interest. Dozens of rounds of evolution can occur in a single day of PACE without human intervention. Using PACE, we evolved T7 RNA polymerase (RNAP) variants that recognize a distinct promoter, initiate transcripts with ATP instead of GTP, and initiate transcripts with CTP. In one example, PACE executed 200 rounds of protein evolution over the course of 8?days. Starting from undetectable activity levels in two of these cases, enzymes with each of the three target activities emerged in less than 1?week of PACE. In all three cases, PACE-evolved polymerase activities exceeded or were comparable to that of the wild-type T7 RNAP on its wild-type promoter, representing improvements of up to several hundred-fold. By greatly accelerating laboratory evolution, PACE may provide solutions to otherwise intractable directed evolution problems and address novel questions about molecular evolution.
