Programmable Artificial Cells Using Histamine-Responsive Synthetic Riboswitch

Artificial cells
that encapsulate DNA-programmable protein expression
machinery are emerging as an attractive platform for studying fundamental
cellular properties and applications in synthetic biology. However,
interfacing these artificial cells with the complex and dynamic chemical
environment remains a major and urgent challenge. We demonstrate that
the repertoire of molecules that artificial cells respond to can be
expanded by synthetic RNA-based gene switches, or riboswitches. We
isolated an RNA aptamer that binds histamine with high affinity and
specificity and used it to design robust riboswitches that activate
protein expression in the presence of histamine. Finally, the riboswitches
were incorporated in artificial cells to achieve controlled release
of an encapsulated small molecule and to implement a self-destructive
kill-switch. Synthetic riboswitches should serve as modular and versatile
interfaces to link artificial cell phenotypes with the complex chemical
environment.