Enhanced Regulation of Prokaryotic Gene Expression By a Eukaryotic Transcriptional Activator

Expanding the genetic toolbox for prokaryotic synthetic biology is a promising strategy for enhancing the dynamic range of gene expression and enabling new engineered applications for research and biomedicine. Currently in the field of prokaryotic synthetic biology, the complexity of genetic circuits is restricted by the number of activatable regulatory elements. Here, we reverse the current trend of moving genetic parts from prokaryotes to eukaryotes and demonstrate that the fungal zinc cluster protein qa-1f (QF) and its corresponding 16bp DNA-binding sequence can be moved to E. coli to introduce transcriptional activation, in addition to tight off states. We further demonstrate that the QF protein can be used in genetic devices that respond to low input levels with robust and sustained output signals. Collectively, we show that eukaryotic gene regulatory elements are functional in prokaryotes and establish a versatile and broadly applicable approach for constructing genetic circuits with complex functions. These new genetic tools hold the potential to improve biotechnology applications for medical science and research.