Regulatory Tools for Controlling Gene Expression in Cyanobacteria

Abstract

Cyanobacteria are attractive hosts for converting carbon dioxide and sunlight into desirable chemical products. To engineer these organisms and manipulate their metabolic pathways, the biotechnology community has developed genetic tools to control gene expression. Many native cyanobacterial promoters and related sequence elements have been used to regulate genes of interest, and heterologous tools that use non-native small molecules to induce gene expression have been demonstrated. Overall, IPTG-based induction systems seem to be leaky and initially demonstrate small dynamic ranges in cyanobacteria. Consequently, a variety of other induction systems have been optimized to enable tighter control of gene expression. Tools require significant optimization because they function quite differently in cyanobacteria when compared to analogous use in model heterotrophs. We hypothesize that these differences are due to fundamental differences in physiology between organisms. This review is not intended to summarize all known products made in cyanobacteria nor the performance (titer, rate, yield) of individual strains, but instead will focus on the genetic tools and the inherent aspects of cellular physiology that influence gene expression in cyanobacteria.

Keywords: Genome editing; Induction system; Promoter; Termination.

Figure 1.

Overview of key factors governing gene expression.

Figure 2.

Fold induction ratios from inducible systems in cyanobacteria. We’ve color-coded bars by inducer (IPTG, aTc, metals, and theophylline), and separated them by induction mechanism (transcription vs translation). The organism and citation can be found below the bar.

Figure 3.

Organization and transcripts observed from cpc operons in PCC 7002 and PCC 7120. Genes are color-coded for their functions (red: structural components, blue: linker proteins, and green: attachment enzymes). Promoters are marked as well as regions that predicted to form significant secondary structures. Observed transcripts are marked below with the thickness indicating relative abundance.