TY - JOUR
T1 - Dynamic control in metabolic engineering
T2 - Theories, tools, and applications
AU - Hartline, Christopher J.
AU - Schmitz, Alexander C.
AU - Han, Yichao
AU - Zhang, Fuzhong
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.
AB - Metabolic engineering has allowed the production of a diverse number of valuable chemicals using microbial organisms. Many biological challenges for improving bio-production exist which limit performance and slow the commercialization of metabolically engineered systems. Dynamic metabolic engineering is a rapidly developing field that seeks to address these challenges through the design of genetically encoded metabolic control systems which allow cells to autonomously adjust their flux in response to their external and internal metabolic state. This review first discusses theoretical works which provide mechanistic insights and design choices for dynamic control systems including two-stage, continuous, and population behavior control strategies. Next, we summarize molecular mechanisms for various sensors and actuators which enable dynamic metabolic control in microbial systems. Finally, important applications of dynamic control to the production of several metabolite products are highlighted, including fatty acids, aromatics, and terpene compounds. Altogether, this review provides a comprehensive overview of the progress, advances, and prospects in the design of dynamic control systems for improved titer, rate, and yield metrics in metabolic engineering.
KW - Biosensors
KW - Dynamic metabolic control
KW - Dynamic metabolic engineering
KW - Genetic circuits
KW - Synthetic biology
UR - http://www.scopus.com/inward/record.url?scp=85092207307&partnerID=8YFLogxK
U2 - 10.1016/j.ymben.2020.08.015
DO - 10.1016/j.ymben.2020.08.015
M3 - Review article
C2 - 32927059
AN - SCOPUS:85092207307
SN - 1096-7176
VL - 63
SP - 126
EP - 140
JO - Metabolic Engineering
JF - Metabolic Engineering
ER -