期刊
ACS SYNTHETIC BIOLOGY
卷 4, 期 2, 页码 107-115出版社
AMER CHEMICAL SOC
DOI: 10.1021/sb400201u
关键词
synthetic biology; metabolic engineering; dynamic control; RNA device; simulation
资金
- Molecular Engineering & Sciences Institute
- University of Washington
- National Science Foundation
Engineered metabolic pathways can be augmented with dynamic regulatory controllers to increase production titers by minimizing toxicity and helping cells maintain homeostasis. We investigated the potential for dynamic RNA based genetic control systems to increase production through simulation analysis of an engineered p-aminostyrene (p-AS) pathway in E coli. To map the entire design space, we formulated 729 unique mechanistic models corresponding to all of the possible control topologies and mechanistic implementations in the system under study. Two thousand sampled simulations were performed for each of the 729 system designs to relate the potential effects of dynamic control to increases in p-AS production (total of 3 x 10(6)simulations). Our analysis indicates that dynamic control strategies employing aptazyme-regulated expression devices (aREDs) can yield >10-fold improvements over static control. We uncovered generalizable trends in successful control architectures and found that highly performing RNA based control systems are experimentally tractable. Analyzing the metabolic control state space to predict optimal genetic control strategies promises to enhance the design of metabolic pathways.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据