Dynamic metabolic control: towards precision engineering of metabolism

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Title: Dynamic metabolic control: towards precision engineering of metabolism
Author(s): Liu, D
Mannan, AA
Han, Y
Oyarzun, DA
Zhang, F
Item 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.
Publication Date: 1-Jul-2018
Date of Acceptance: 12-Jan-2018
URI: http://hdl.handle.net/10044/1/56656
DOI: https://dx.doi.org/10.1007/s10295-018-2013-9
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/Funder: Human Frontier Science Program
Funder's Grant Number: RGY-0076/2015
Keywords: Biosensors
Dynamic metabolic control
Genetic circuits
Model-based design
Synthetic biology
1003 Industrial Biotechnology
0908 Food Sciences
Publication Status: Published
Embargo Date: 2019-01-29
Online Publication Date: 2018-01-29
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Natural Sciences

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