Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Trends Biotechnol. 2021 Jan;39(1):59-71. doi: 10.1016/j.tibtech.2020.05.013. Epub 2020 Jun 22.
Synthetic biology strives to reliably control cellular behavior, typically in the form of user-designed interactions of biological components to produce a predetermined output. Engineered circuit components are frequently derived from natural sources and are therefore often hampered by inadvertent interactions with host machinery, most notably within the host central dogma. Reliable and predictable gene circuits require the targeted reduction or elimination of these undesirable interactions to mitigate negative consequences on host fitness and develop context-independent bioactivities. Here, we review recent advances in biological orthogonalization, namely the insulation of researcher-dictated bioactivities from host processes, with a focus on systematic developments that may culminate in the creation of an orthogonal central dogma and novel cellular functions.
合成生物学致力于可靠地控制细胞行为，通常以用户设计的生物组件相互作用的形式来产生预定的输出。工程化的电路组件通常源自天然来源，因此经常受到与宿主机制的意外相互作用的阻碍，尤其是在宿主中心法则内。可靠和可预测的基因电路需要有针对性地减少或消除这些不理想的相互作用，以减轻对宿主适应性的负面影响，并开发与上下文无关的生物活性。在这里，我们回顾了生物正交化的最新进展，即研究人员规定的生物活性与宿主过程的隔离，重点介绍了可能最终导致创建正交中心法则和新型细胞功能的系统发展。
