Modular Design of transcriptional regulatory parts

Yeqing Zong1, Haoqian Zhang2, Xiangyu Ji1, Qi Ouyang2, Chunbo Lou1

1CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of

Microbiology, Chinese Academy of Sciences, Beijing, China

2Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences,, School of

Physics, Peking University, Beijng, 100871, China

Abstract

Predictably assembling genetic circuits requires a diversity of compositional DNA parts encoding defined functions. However, when assembling the parts, their defined functions are fragile, and usually interfered by other parts and their host cells. Several strategies have been developed to insulate some specific parts from their genetic context (e.g. RBS). Here, we describe a modular architecture to insulate the operators from their cognate promoters (recognized by T7 RNAP or sigma ECF11) in E. coli. In the modular architecture, the regulatory functions of different operators were described by a novel mathematical framework; meanwhile promoterâ??s activities were independent of the operators. More than 1000 transcriptional regulatory parts could be combinatorially constructed from a promoter and operator library, and their regulatory functions are easily predicted by a simple model without any fitting parameter. The versatile modular parts library is powerful toolbox to facilitate the construction of sophisticated genetic circuits.