Sensitive cells: enabling tools for static and dynamic control of microbial metabolic pathways. (December 2015)

• Record Type: Journal Article
• Authors: Cress, Brady F; Trantas, Emmanouil A; Ververidis, Filippos; Linhardt, Robert J; Koffas, Mattheos AG
• Is Part Of: Current opinion in biotechnology. Volume 36(2015)
• Page Start: 205
• Page End: 214
• Publication Date: 2015-12
• Subjects: Biotechnology -- Periodicals; 660.6
• DOI: 10.1016/j.copbio.2015.09.007
• Languages: English
• ISSNs: 0958-1669

Abstract

Graphical abstract: Highlights: Recently developed genome engineering tools facilitate pathway control. Novel genetic regulators enable multi-level static and dynamic control. State-of-the-art applications of dynamic metabolic control are discussed. Static and dynamic control strategies will likely maintain distinct niches. We predict dynamic genetic control circuits interfacing with host genomes. Abstract : Natural metabolic pathways are dynamically regulated at the transcriptional, translational, and protein levels. Despite this, traditional pathway engineering has relied on static control strategies to engender changes in metabolism, most likely due to ease of implementation and perceived predictability of design outcome. Increasingly in recent years, however, metabolic engineers have drawn inspiration from natural systems and have begun to harness dynamically controlled regulatory machinery to improve design of engineered microorganisms for production of specialty and commodity chemicals. Here, we review recent enabling technologies for engineering static control over pathway expression levels, and we discuss state-of-the-art dynamic control strategies that have yielded improved outcomes in the field of microbial metabolic engineering. Furthermore, we emphasize design of a novel class of genetically encoded controllers that will facilitate automatic, transient tuning of synthetic and endogenous pathways.