Boosting Secondary Metabolite Production and Discovery through the Engineering of Novel Microbial Biosensors

Figure 1

Main strategies to engineer novel control systems for SM production/discovery. As a central approach, several works have focused on the development of novel transcriptional control modules such as those based on the strong T7 RNA polymerase/T7 promoter. On a different perspective, natural or engineered small metabolite-responsive regulators have been used to control gene expression in response to a ligand of interest. More sophisticated approaches have focused on combining engineered ligand-binding and DNA-binding domains to create new expression devices. An entirely novel approach has been the usage of VHH antibody domains to couple ligand recognition to gene expression elements. Additionally, gene expression modulation using modified CRISPR/Cas9 modules is becoming more frequent every day. Finally, posttranslational regulation of protein production has been addressed through either the engineering of novel ligand-specific riboswitches or temperature responsive regulatory elements (thermometers). A full description of these main cases is presented in the text. GOI: gene of interest; O: operator, a cis-regulatory element; T7P: T7 promoter; RBS: ribosome binding site.