《生命科学》 2011, 23(9): 860-868

生物元件的挖掘、改造与标准化

王钱福，严　兴，魏　维，张　磊，钱昌丽，周志华^*

(中国科学院上海生命科学研究院植物生理生态研究所，中科院合成生物学重点实验室，上海 200032)

摘　要：摘　要：生物元件是合成生物学中的三大基本要素之一，是合成生物学的基石。现阶段，生物元件的挖掘、鉴定和改造仍然是合成生物学领域的重要研究方向之一。合成生物学与基因工程和代谢工程最显著的差别在于能够将大量的生物元件进行快速、随意的组装，而实现这一目标的前提是将生物元件标准化。目前，已经有大量基因组被解析，通过这些基因组数据库的注释与功能验证，并借助于各种生物信息学软件预测启动子、终止子、操纵子、转录因子和转录因子结合位点、核糖体结合位点以及蛋白质编码区等部件，为合成生物学提供丰富的生物元件信息资源。随着元基因组技术的兴起，大量未培养微生物中的基因和基因簇信息被解析，使得我们可以从占自然界中实际存在微生物总数99％的未知微生物中挖掘更多的生物元件。另外，生物元件可以从自然界分离出来，也可以对天然生物元件进行修饰、重组和改造后得到新的元件。酵母是异源蛋白表达的通用宿主和生物基产品生产的细胞工厂，但其本身可用的启动子非常有限，近年来各国学者在酵母启动子改造和文库构建方面做了很多工作，该文也将概述酵母启动子改造和在合成生物生物学研究领域中的应用方面的研究进展。
关键词：合成生物学；生物元件；基因组；元基因组；启动子； 文库构建

Screening， modification and standardization of biological parts for synthesis biology

WANG Qian-Fu， YAN Xing， WEI Wei， ZHANG Lei， QIAN Chang-Li， ZHOU Zhi-Hua^*

(Key Laboratory of Synthetic Biology， Institute of Plant Physiologyl and Ecology， Shanghai Institutes for Biological Sciences， Chinese Academy of Sciences， Shanghai 200032， China)

Abstract: Abstract: Biological part is the foundation for synthetic biology. Seeking， defining and modifying of new biological parts are attracting common attentions. The most significant difference between synthetic biology and genetic engineering or metabolic engineering must be that the interchangeable biological parts are used and assembled quickly in synthetic biology， which had better to be standardized previously. With more and more genomes of different organisms being sequenced， parts such as promoters， terminators， operons， transcriptional factors and transcriptional factor binding sites， ribosome binding sites and protein encoding regions could be annotated by different bioinformatics tools. Owing to the development of metagenomic technology， vast information about the genes and gene clusters of the remaining 99% uncultured microorganisms in nature were explored and a lot of new biological parts could be mined from natural resources directly. Of course， the biological part originated from nature need be modified， reconstructed and improved before it shows highly compatible in a synthetic module or biological system. Saccharomyces cerevisiae was widely used as the general host for heterologous proteins expression as well as cell factory for producing biobased products. However， only a few promoters could be applied in S. cerevisiae. Many efforts to modify promoters and establish promoter mutant libraries for S. cerevisiae have been tried recently. A brief introduction of studies on promoter evolution of S. cerevisiae and its application in synthetic biological field are also included in this manuscript.
Key words: synthetic biology; biological parts; genome; metagenome; promoter; library construction