Deconstruction of complex protein signaling switches: a roadmap toward engineering higher ‐order gene regulators

The control of gene expression is an important tool for metabolic engineering, the design of synthetic gene networks, gene‐function analysis, and protein manufacturing. The most successful approaches to date are based on modulating messenger RNA (mRNA) synthesis via their inducible coupling to transcriptional effectors, which requires biosensing functionality. A hallmark of biological sensing is the conversion of an exogenous signal, usually a small molecule or environmental cue such as a protein–ligand interaction, into a useful output or response. One of the most utilized regulatory proteins is the lactose repressor (LacI). In this review we will (1) explore the mechanochemical structure–function relationship of LacI; (2) discuss how the physical attributes of LacI can be leveraged to identify and understand other regulatory proteins; (3) investigate the designability (tunability) of LacI; (4) discuss the potential of the modular design of novel regulatory proteins, fashioned after the topology and mechanochemical properties of LacI. For further resources related to this article, please visit the WIREs website. Modular engineering of a hypothetical co‐repressor using components scavenged from the versatile LacI/GalR repressor family reviewed here
Source: Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology - Category: Nanotechnology Authors: Tags: Advanced Review Source Type: research