Mediating Ribosomal Competition by Splitting Pools

被引:8
|
作者
Miller, Jared [1 ]
Al-Radhawi, M. Ali [1 ]
Sontag, Eduardo D. [1 ,2 ,3 ]
机构
[1] Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA
[2] Northeastern Univ, Dept Bioengn, Boston, MA 02115 USA
[3] Harvard Med Sch, Lab Syst Pharmacol, Boston, MA 02115 USA
来源
IEEE CONTROL SYSTEMS LETTERS | 2021年 / 5卷 / 05期
基金
美国国家科学基金会;
关键词
Proteins; Steady-state; Integrated circuit modeling; RNA; Amino acids; Throughput; Stability analysis; Synthetic biology; orthogonal ribosome flow model; robust Lyapunov functions; translation rate optimization; LYAPUNOV FUNCTIONS; REACTION NETWORKS; STABILITY;
D O I
10.1109/LCSYS.2020.3041213
中图分类号
TP [自动化技术、计算机技术];
学科分类号
0812 ;
摘要
Synthetic biology constructs often rely upon the introduction of "circuit" genes into host cells, in order to express novel proteins and thus endow the host with a desired behavior. The expression of these new genes "consumes" existing resources in the cell, such as ATP, RNA polymerase, amino acids, and ribosomes. Ribosomal competition among strands of mRNA may be described by a system of nonlinear ODEs called the Ribosomal Flow Model (RFM). The competition for resources between host and circuit genes can be ameliorated by splitting the ribosome pool by use of orthogonal ribosomes, where the circuit genes are exclusively translated by mutated ribosomes. In this letter, the RFM system is extended to include orthogonal ribosome competition. This Orthogonal Ribosomal Flow Model (ORFM) is proven to be stable through the use of Robust Lyapunov Functions. The optimization problem of maximizing the weighted protein translation rate by adjusting allocation of ribosomal species is formulated.
引用
收藏
页码:1555 / 1560
页数:6
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