Mediating Ribosomal Competition by Splitting Pools

Jared Miller, M. Ali Al-Radhawi, Eduardo D. Sontag

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number9273048
Pages (from-to)1555-1560
Number of pages6
JournalIEEE Control Systems Letters
Volume5
Issue number5
DOIs
StatePublished - Nov 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Control and Systems Engineering
  • Control and Optimization

Keywords

  • Synthetic biology
  • orthogonal ribosome flow model
  • robust Lyapunov functions
  • translation rate optimization

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