Liu, Di, Mannan, Ahmad A., Han, Yichao, Oyarzún, Diego A. and Zhang, Fuzhong (2018) Dynamic metabolic control : towards precision engineering of metabolism. Journal of Industrial Microbiology & Biotechnology, 45 (7). pp. 535-543. 9. doi:10.1007/s10295-018-2013-9 ISSN 1476-5535.

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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.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH):	Microorganisms -- Metabolism -- Regulation -- Industrial applications, Biosensors, Synthetic biology
Journal or Publication Title:	Journal of Industrial Microbiology & Biotechnology
Publisher:	Springer
ISSN:	1476-5535
Official Date:	1 July 2018
Dates:	Date Event 1 July 2018 Published 1 January 2018 Available 13 January 2018 Accepted 2 November 2017 Submitted
Volume:	45
Number:	7
Page Range:	pp. 535-543
Article Number:	9
DOI:	10.1007/s10295-018-2013-9
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	31 May 2018
Date of first compliant Open Access:	29 January 2019
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID RGY0076-2015 Human Frontier Science Program http://dx.doi.org/10.13039/100004412 MCB1453147 National Science Foundation http://dx.doi.org/10.13039/100000001
Open Access Version:	Other

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