合成生物學利用數學模型來描述生物系統的基因表現，並且將設計的合成基因電路實現在活體細胞中以達到各式各樣的應用。在此研究中，根據良好特性的啟動子-核糖體結合位元件庫及串接基因電路拓樸，匹配期望的輸入/輸出響應的外部可控強健生物濾波器被設計出來。在合成生物領域中，生物濾波系統作為一個功能強大的檢測器或感測器，可以感測不同分子訊號，並且只有在輸入分子訊號的濃度高於或低於指定的門檻才會產生特定的輸出響應。在這裡，強健生物濾波器的設計方法被概括為三個步驟。第一，經由非線性參數估計方法識別三種啟動子-核糖體結合位元件的定性與定量特性，建立了良好特性的啟動子-核糖體結合位元件庫。第二，功能作為生物濾波器的合成基因電路被分解成三個串接的基因調控模組，每個模組包含一個從對應元件庫中選擇的啟動子-核糖體結合位元件。最後，根據系統化方法，藉由搜尋啟動子-核糖體結合位元件庫與控制誘導物濃度，強健外部可調生物濾波器被設計與指定輸入/輸出濾波響應達到最佳匹配。在此研究中描述的生物濾波器可以單獨設計以檢測不同金屬離子的殘留量。此外在合成生物學中，藉由模組化的概念，個別的生物濾波器可被整合成更高階的系統以產生廣泛的生物應用。

Synthetic biology employs the mathematical models to capture the gene expression of engineered biological systems and implements the designed synthetic gene circuits in living cells for a variety of applications. In this study, robust biological filters with an external control to match a desired input/output (I/O) response are engineered based on the well-characterized promoter-RBS libraries and a cascade gene circuit topology. In the synthetic biological field, the biological filter system serves as a powerful detector or sensor that can sense different molecular signals and produces a specific output response only if the concentration of the input molecular signal is higher or lower than a specified threshold. Here the design approach of robust biological filters is summarized to three steps. Firstly, several well-characterized promoter-RBS libraries are established by identifying and collecting the quantitative and qualitative characteristics of three kinds of promoter-RBS components via nonlinear parameter estimation method. Secondly, the synthetic gene circuit functioned as the biological filter is decomposed into three cascade gene regulatory modules, and an adequate promoter-RBS component is selected for each module from the corresponding promoter-RBS library. Finally, based on the proposed systematic method, a robust externally tunable biological filter is engineered by searching the promoter-RBS component libraries and a control inducer concentration library to achieve the optimal matching with the specified I/O filtering response. The biological filters design in this study might be applicable to detect the residual of different metallic ions. In addition, the designed biological filters can be integrated into higher-order systems with the concept of modularity for a wide range of biological applications in synthetic biology.

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