Natural and synthetic DNA transcriptional terminators that efficiently stop transcription and enable the design of more complex genetic pathways are reported in a paper published this week in Nature Methods.

To engineer biological pathways, scientists often combine different genes on a stretch of DNA and then need to precisely define where each gene begins and ends so that these genes can be correctly transcribed and translated. Weak termination fails to halt transcription where required and, thus, creates nonfunctional gene products, but to date only a handful of strong terminators exist. This shortage limits the complexity of circuit design because terminators used multiple times in the same design tend to recombine with each other and thereby disrupt the order of the circuit.

Christopher Voigt and colleagues screened hundreds of terminators that occur naturally in the bacterium Escherichia coli. They then determined design principles and applied them to construct hundreds of terminators, each with a quantitatively defined strength. The authors engineer a transcriptional logic gate that is still stable after 70 cell doublings.