Elena Claudia, Ravasi Pablo, Castelli María E, Peirú Salvador, Menzella Hugo G
Genetic Engineering and Fermentation Technology, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario-Conicet Rosario, Argentina.
Front Microbiol. 2014 Feb 4;5:21. doi: 10.3389/fmicb.2014.00021. eCollection 2014.
The efficient production of functional proteins in heterologous hosts is one of the major bases of modern biotechnology. Unfortunately, many genes are difficult to express outside their original context. Due to their apparent "silent" nature, synonymous codon substitutions have long been thought to be trivial. In recent years, this dogma has been refuted by evidence that codon replacement can have a significant impact on gene expression levels and protein folding. In the past decade, considerable advances in the speed and cost of gene synthesis have facilitated the complete redesign of entire gene sequences, dramatically improving the likelihood of high protein expression. This technology significantly impacts the economic feasibility of microbial-based biotechnological processes by, for example, increasing the volumetric productivities of recombinant proteins or facilitating the redesign of novel biosynthetic routes for the production of metabolites. This review discusses the current applications of this technology, particularly those regarding the production of small molecules and industrially relevant recombinant enzymes. Suggestions for future research and potential uses are provided as well.
在异源宿主中高效生产功能蛋白是现代生物技术的主要基础之一。不幸的是，许多基因在其原始环境之外很难表达。由于其明显的“沉默”性质，同义密码子替换长期以来一直被认为是微不足道的。近年来，这一教条已被证据反驳，即密码子替换可对基因表达水平和蛋白质折叠产生重大影响。在过去十年中，基因合成速度和成本方面的显著进展促进了整个基因序列的完全重新设计，极大地提高了高蛋白表达的可能性。例如，通过提高重组蛋白的体积生产力或促进用于生产代谢物的新型生物合成途径的重新设计，该技术显著影响基于微生物的生物技术过程的经济可行性。本综述讨论了该技术的当前应用，特别是那些与小分子和工业相关重组酶生产有关的应用。还提供了未来研究和潜在用途的建议。
