Diversity, versatility and complexity of bacterial gene regulation mechanisms: opportunities and drawbacks for applications in synthetic biology

Gene expression occurs in two essential steps, transcription and translation. In bacteria, the two processes are tightly coupled in time and space, and highly regulated. Tight regulation of gene expression is crucial. It limits wasteful consumption of resources and energy, prevents accumulation of potentially growth inhibiting reaction intermediates, and sustains the fitness and potential virulence of the organism in a fluctuating, competitive and frequently stressful environment. Since the onset of studies on regulation of enzyme synthesis, numerous distinct regulatory mechanisms modulating transcription and/or translation have been discovered. Mostly various regulatory mechanisms operating at different levels in the flow of genetic information are used in combination to control and modulate the expression of a single gene or operon. Here, we provide an extensive overview of the very diverse and versatile bacterial gene regulatory mechanisms with major emphasis on their combined occurrence, intricate intertwinement, and versatility. Furthermore, we discuss the potential of well-characterized basal expression and regulatory elements in synthetic biology applications, where they may ensure orthogonal, predictable, and tunable expression of (heterologous) target genes and pathways, aiming at a minimal burden for the host.