Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, USA.
Biotechnol J. 2013 Jan;8(1):46-58. doi: 10.1002/biot.201200120. Epub 2012 Aug 14.
Synthetic control of gene expression is critical for metabolic engineering efforts. Specifically, precise control of key pathway enzymes (heterologous or native) can help maximize product formation. The fundamental level of transcriptional control takes place at promoter elements that drive gene expression. Endogenous promoters are limited in that they do not fully sample the complete continuum of transcriptional control, and do not maximize the transcription levels achievable within an organism. To address this issue, several attempts at promoter engineering have shown great promise both in expanding the cell-wide transcriptional capacity of an organism and in enabling tunable levels of gene expression. Thus, this review highlights the recent advances and approaches for altering gene expression control at the promoter level. Furthermore, we propose that recent advances in the understanding of transcription factors and their DNA-binding sites will enable rational and predictive control of gene expression.
基因表达的人工控制对于代谢工程的努力至关重要。具体来说,对关键途径酶(异源或天然)的精确控制有助于最大限度地提高产物形成。转录控制的基本水平发生在驱动基因表达的启动子元件上。内源性启动子的局限性在于它们不能完全采样完整的转录控制连续体,也不能最大限度地提高生物体中可实现的转录水平。为了解决这个问题,几种启动子工程的尝试在扩大生物体的全细胞转录能力和实现基因表达的可调水平方面都显示出了巨大的潜力。因此,本综述强调了在启动子水平上改变基因表达控制的最新进展和方法。此外,我们提出,对转录因子及其 DNA 结合位点的理解的最新进展将能够实现基因表达的合理和预测性控制。