Dynamic metabolic control: towards precision engineering of metabolism

Di Liu, Ahmad A. Mannan, Yichao Han, Diego A. Oyarzún, Fuzhong Zhang
2018 Journal of Industrial Microbiology & Biotechnology  
12 Advances in metabolic engineering have led to the synthesis of a wide variety of valuable 13 chemicals in microorganisms. The key to commercializing these processes is the improvement of 14 titer, productivity, yield, and robustness. Traditional approaches to enhancing production uses 15 the "push-pull-block" strategy that modulates enzyme expression under static control. However, 16 strains are often optimized for specific laboratory set-up and are sensitive to environmental 17
more » ... Exposure to sub-optimal growth conditions during large-scale fermentation often 18 reduces their production capacity. Moreover, static control of engineered pathways may 19 imbalance cofactors or cause the accumulation of toxic intermediates, which imposes burden on 20 the host and results in decreased production. To overcome these problems, the last decade has 21 witnessed the emergence of a new technology that uses synthetic regulation to control 22 heterologous pathways dynamically, in ways akin to regulatory networks found in nature. Here 23 we review natural metabolic control strategies and recent developments in how they inspire the 24 engineering of dynamically regulated pathways. We further discuss the challenges of designing 25 and engineering dynamic control and highlight how model-based design can provide a powerful 26 formalism to engineer dynamic control circuits, which together with the tools of synthetic 27 biology, can work to enhance microbial production. 28 29
doi:10.1007/s10295-018-2013-9 pmid:29380150 fatcat:nc7sx54q6jdexemvx33cucgodq