Back to Search Start Over

Gene Expression Space Shapes the Bioprocess Trade-Offs among Titer, Yield and Productivity

Authors :
Fernando N. Santos-Navarro
Yadira Boada
Alejandro Vignoni
Jesús Picó
Source :
Applied Sciences, Vol 11, Iss 13, p 5859 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

Optimal gene expression is central for the development of both bacterial expression systems for heterologous protein production, and microbial cell factories for industrial metabolite production. Our goal is to fulfill industry-level overproduction demands optimally, as measured by the following key performance metrics: titer, productivity rate, and yield (TRY). Here we use a multiscale model incorporating the dynamics of (i) the cell population in the bioreactor, (ii) the substrate uptake and (iii) the interaction between the cell host and expression of the protein of interest. Our model predicts cell growth rate and cell mass distribution between enzymes of interest and host enzymes as a function of substrate uptake and the following main lab-accessible gene expression-related characteristics: promoter strength, gene copy number and ribosome binding site strength. We evaluated the differential roles of gene transcription and translation in shaping TRY trade-offs for a wide range of expression levels and the sensitivity of the TRY space to variations in substrate availability. Our results show that, at low expression levels, gene transcription mainly defined TRY, and gene translation had a limited effect; whereas, at high expression levels, TRY depended on the product of both, in agreement with experiments in the literature.

Details

Language :
English
ISSN :
11135859 and 20763417
Volume :
11
Issue :
13
Database :
Directory of Open Access Journals
Journal :
Applied Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.32acfa7597c0494187cd00f01d03e635
Document Type :
article
Full Text :
https://doi.org/10.3390/app11135859