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Reliably Engineering and Controlling Stable Optogenetic Gene Circuits in Mammalian Cells

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Controlling and exploiting cell-to-cell variation in metabolic engineering.

Tiebin Wang¹, Mary J Dunlop²

¹Molecular Biology, Cell Biology & Biochemistry Program, Boston University, Boston, MA, USA; Biological Design Center, Boston University, Boston, MA, USA.

Current Opinion in Biotechnology

|September 28, 2018

Summary

Cell-to-cell variation impacts production in metabolic engineering. Strategies managing this diversity can improve yields of biosynthetic products, offering a novel approach to enhance engineered cell performance.

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Area of Science:

Synthetic Biology
Metabolic Engineering
Cellular Phenotypes

Background:

Cellular phenotypes vary due to environmental, genetic, and stochastic factors.
This cell-to-cell variation is critical in metabolic engineering, affecting production yields.
Heterogeneous production among engineered cells necessitates strategies to manage diversity.

Purpose of the Study:

To review the origins of cell-to-cell variation in metabolic engineering.
To discuss strategies for managing cell-to-cell variation to improve engineered cell performance.
To explore methods to diminish, accept, or exploit cellular diversity for enhanced production.

Main Methods:

Literature review of studies on cell-to-cell variation in metabolic engineering.
Analysis of strategies for controlling or utilizing cellular diversity.
Identification of research trends and future directions in the field.

Main Results:

Cellular diversity arises from local environment, genetic differences, and gene expression noise.
Managing cell-to-cell variation can significantly improve yields of biosynthetic products.
Novel strategies are emerging to control, accept, or exploit cellular variation.

Conclusions:

Controlling cell-to-cell variation presents a promising avenue for improving metabolic engineering outcomes.
Understanding and manipulating cellular diversity is key to optimizing engineered cell performance.
Further research into managing phenotypic heterogeneity will advance biosynthetic production.