A Modelling Framework Linking Resource-Based Stochastic Translation to the Optimal Design of Synthetic Constructs.

ABSTRACT: The effect of gene expression burden on engineered cells has motivated the use of "whole-cell models" (WCMs) that use shared cellular resources to predict how unnatural gene expression affects cell growth. A common problem with many WCMs is their inability to capture translation in sufficient detail to consider the impact of ribosomal queue formation on mRNA transcripts. To address this, we have built a "stochastic cell calculator" (StoCellAtor) that combines a modified TASEP with a stochastic implementation of an existing WCM. We show how our framework can be used to link a synthetic construct's modular design (promoter, ribosome binding site (RBS) and codon composition) to protein yield during continuous culture, with a particular focus on the effects of low-efficiency codons and their i

SUBMITTER: Sarvari P 

PROVIDER: S-EPMC7826857 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature