Dynamic metabolic control: towards precision engineering of metabolism
File(s)
Accepted version
Author(s)
Liu, D
Mannan, AA
Han, Y
Oyarzun, DA
Zhang, F
Type
Journal Article
Abstract
Advances in metabolic engineering have led to the synthesis of a wide variety of valuable chemicals in microorganisms. The key to commercializing these processes is the improvement of titer, productivity, yield, and robustness. Traditional approaches to enhancing production use the “push–pull-block” strategy that modulates enzyme expression under static control. However, strains are often optimized for specific laboratory set-up and are sensitive to environmental fluctuations. Exposure to sub-optimal growth conditions during large-scale fermentation often reduces their production capacity. Moreover, static control of engineered pathways may imbalance cofactors or cause the accumulation of toxic intermediates, which imposes burden on the host and results in decreased production. To overcome these problems, the last decade has witnessed the emergence of a new technology that uses synthetic regulation to control heterologous pathways dynamically, in ways akin to regulatory networks found in nature. Here, we review natural metabolic control strategies and recent developments in how they inspire the engineering of dynamically regulated pathways. We further discuss the challenges of designing and engineering dynamic control and highlight how model-based design can provide a powerful formalism to engineer dynamic control circuits, which together with the tools of synthetic biology, can work to enhance microbial production.
Date Issued
2018-07-01
Date Acceptance
2018-01-12
Citation
Journal of Industrial Microbiology and Biotechnology, 2018, 45 (7), pp.535-543
ISSN
1367-5435
Publisher
Springer Verlag
Start Page
535
End Page
543
Journal / Book Title
Journal of Industrial Microbiology and Biotechnology
Volume
45
Issue
7
Copyright Statement
© Society for Industrial Microbiology and Biotechnology 2018. The final publication is available at Springer via https://link.springer.com/article/10.1007%2Fs10295-018-2013-9
Sponsor
Human Frontier Science Program
Grant Number
RGY-0076/2015
Subjects
Biosensors
Dynamic metabolic control
Genetic circuits
Model-based design
Synthetic biology
1003 Industrial Biotechnology
0908 Food Sciences
Biotechnology
Publication Status
Published
Date Publish Online
2018-01-29