基因设计对重组蛋白表达的影响研究进展

Effects of gene design on recombinant protein expression: a review

摘要:

利用异源表达系统生产重组蛋白已成为现代基因工程和生物工程研究热点和重点。但是研究者发现并非所有的基因都能在异源宿主中高效表达，除了宿主、分泌途径、启动子等因素外，基因自身的序列也蕴含了多种影响蛋白表达的因素，如密码子偏爱性，密码子对偏爱性，GC含量，mRNA二级结构，mRNA稳定性等。从基因设计的角度对影响蛋白表达的因素和方法进行了综述，尤其是对密码子优化和密码子对优化，详细讨论了与传统基因优化理念截然不同的密码子协调化及密码子对协调化等最新进展。

Abstract:

It has become a hotspot and keystone in gene engineering and bioengineering to produce recombinant proteins through heterologous expression systems. Unfortunately, not all the genes could be successfully and effectively expressed in heterologous hosts. The role of gene itself in regulating translation process through its intrinsic sequence characteristics such as codon bias, codon pair bias, GC content, mRNA secondary structure and mRNA stability, has been gradually elucidated. Here we review these factors that influenc the translation processes and their corresponding optimization methods in the process of gene design. We emphatically discussed codon bias and codon pair bias and their optimization methods. In particular, the latest theories of codon harmonization and codon pair harmonization were discussed and compared with the traditional codon and codon pair optimization strategies in gene design.