**1. Introduction**

Controlling the processes or functioning of biological systems has profound implications in biotechnological and other applications [1]. By controlling gene expression, cell behavior and responses to environmental cues can, in turn, be regulated. Ever since the dawn of biotechnology, scientists have been searching for new and better methods to specifically modulate gene expression. Biological systems, however, possess the ability to sense and respond to internal or environmental changes through tuning their own genetic networks. For example, they are capable of detecting metabolic stress during foreign protein expression, and in response, express genes that brake or facilitate the process. Cells are also able to receive signaling molecules from their 'neighbors', to then begin functioning as a 'collective' or population by activating certain genetic regulons. In this chapter, gene-regulating technologies of prokaryotes are discussed that intentionally alter the intracellular landscape for protein expression as well as the extracellular microenvironmental state in the vicinity of 'designer' production strains in order to program gene expression and behavior. These techniques incorporate the understanding of cell metabolism and the transcriptome, cell-cell communication (previously reviewed by [2, 3]), and biological redox reactions (previously reviewed by [4]). This chapter will mainly focus on recent advances in how actuation of genes is accomplished in *Escherichia coli* through methods that require only minimal genetic rewiring and the technologies developed on such platforms, for instance those of biosensors and bioelectric devices.
