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浙江大学于浩然课题组BA综述|让定向进化更容易的“热点”

来源: 遇见生物合成 发布: 2022-02-22 505阅读 105评论

近日，浙江大学化学工程与生物工程学院于浩然研究团队与伦敦大学学院Paul A. Dalby教授课题组合作撰写的综述性论文“Hot spots-making directed evolution easier”发表于国际生物技术顶级期刊Biotechnology Advances（IF14.2）。

为了加速蛋白质的进化，定向进化已经成为一种强大的策略，用于设计提升蛋白的特定性质。然而利用易错PCR，DNA shuffling等传统方法构建的突变体文库通常规模非常大，在没有高通量筛选方法的情况下，筛选这种文库是费时、费力和费钱的。另一方面，以结构或序列信息为指导的点饱和突变也已成为蛋白质工程的一种常用方法，该方法旨在构建“小而精”的突变体文库，进一步提高了定向进化的效率。该方法的前提是突变靶点预测是可靠的，突变靶点或热点位置（Hot spots）的预测对于文库的质量和定向进化的效果至关重要。

该项工作概述了可用于蛋白质进化的七种热点位置，主要分为两类：Ⅰ）基于序列的热点，包括CbD (conserved but different) 位点和共进化残基；Ⅱ）基于三维结构的热点，包括活性位点残基、通道位点、灵活位点、与活性中心“耦合”的远端位点和界面位点。热点位置的选择应基于所需改造的蛋白质特性和可用的结构信息进行（表1）。值得注意的是，这些热点只提供了潜在的突变目标，在实际情况中可能需要其他标准来缩小突变位点的范围。该项工作还对预测这些热点位置的计算工具及将其用于酶工程的许多成功案例进行了综述。

表1 热点位置选择指南

论文以浙江大学化学工程与生物工程学院为第一完成单位，论文中相关研究工作得到国家自然科学基金项目（22108245）的资助。

招贤纳士

于浩然博士，浙江大学“百人计划”研究员，博士生导师，浙江大学杭州国际科创中心青年人才卓越计划入选者。本科、硕士毕业于天津大学，博士毕业于伦敦大学学院，归国前就职于伦敦大学学院任博士后研究员。主要研究领域包括蛋白质工程，酶分子智能设计等，在PNAS，ACS Catalysis，Biotechnology Advances等期刊发表10余篇论文。主持国家自然科学基金青年项目、UCL-ZJU国际合作项目等，任英国皇家化学学会Associate member，中国生物工程学会合成生物学分会青年工作组委员等。现招聘酶工程、机器学习、计算机蛋白质设计相关方向博士后1-2名，欢迎感兴趣的同学提供个人简历（包括学习工作经历，主要研究工作，代表性论文等），发送至yuhaoran@zju.edu.cn。

 

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