两种基于细胞资源的生长和部件特性模型有助于合成基因回路的研究和优化
Two Cellular Resource Based Models Linking Growth and Parts Characteristics Aids the Study and Optimization of Synthetic Gene Circuits
摘要：
合成遗传电路开发中的一个主要挑战是电路的异源基因表达与宿主生长速率之间的相互依赖性。增加异源基因表达增加了宿主的负担，导致宿主生长减少;这降低了总体异源蛋白丰度。因此，很难设计出可预测的基因电路。在这里，我们开发了两个生物物理模型，一个为启动子，另一个为RBS，以关联异源基因表达和生长减少。我们在E.大肠杆菌来描述这种负担，即由遗传电路引起的生长减少。为了促进它们在遗传电路设计中的使用，模型的输入是生物部分的共同特征[例如相对启动子强度（RPU）和相对核糖体结合位点强度（RRU）]。模型表明，E.大肠杆菌的生长速率随着遗传电路的RPU / RRU的增加而线性降低;因此，提供了2个方便的模型，以部件特性作为输入来估计生长速率降低，用于在构建之前在计算机中微调遗传电路设计。我们的启动子模型与使用各种遗传电路（单表达盒和双表达盒）的实验具有良好的相关性，相对启动子单位高达3.7，生长率降低60%（平均R2 ~ 0.9）。
英文摘要：
A major challenge in synthetic genetic circuit development is the inter-dependency between heterologous gene expressions by circuits and host's growth rate. Increasing heterologous gene expression increases burden to the host, resulting in host growth reduction; which reduces overall heterologous protein abundance. Hence, it is difficult to design predictable genetic circuits. Here, we develop two biophysical models; one for promoter, another for RBS; to correlate heterologous gene expression and growth reduction. We model cellular resource allocation in E. coli to describe the burden, as growth reduction, caused by genetic circuits. To facilitate their uses in genetic circuit design, inputs to the model are common characteristics of biological parts [e.g. relative promoter strength (RPU) and relative ribosome binding sites strength (RRU)]. The models suggest that E. coli's growth rate reduces linearly with increasing RPU / RRU of the genetic circuits; thus, providing 2 handy models taking parts characteristics as input to estimate growth rate reduction for fine tuning genetic circuit design in silico prior to construction. Our promoter model correlates well with experiments using various genetic circuits, both single and double expression cassettes, up to a relative promoter unit of 3.7 with a 60% growth rate reduction (average R2 ~ 0.9).
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