Using metabolite-responsive gene regulators to improve microbial biosynthesis

作者:Qian Shuai; Cirino Patrick C
来源:Current Opinion in Chemical Engineering, 2016, 14: 93-102.
DOI:10.1016/j.coche.2016.08.020

摘要

In microorganisms, ligand-induced gene regulators (proteins and nucleic acids) orchestrate complex changes in gene expression in response to changes in the cellular environment and metabolic status. This review highlights two increasingly popular applications of these types of regulation systems as genetically-encoded biosensors. As molecular reporters, transcription factors and riboswitches are being used to search gene libraries for enhanced production (or in some cases depletion) of the corresponding ligand. Similar genetic constructions allow for growth-coupled product formation and continuous evolution of strain productivity. Meanwhile, whereas gene expression systems for metabolic engineering have traditionally been static or externally tunable, an expanding toolbox of metabolite-responsive gene regulators coupled with deeper insights into metabolic bottlenecks have given rise to dynamic control over engineered pathways. These synthetic ` sensing' gene circuits balance metabolite flux and enhance strain productivity. Such innovative applications of metabolite biosensors present new directions in metabolic engineering.

  • 出版日期2016-11