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Biologists Develop Worlds Most Complex Synthetic Biology Circuit to Create Programmable Yeast

Using genes as interchangeable parts, synthetic biologists design cellular circuits that can perform new functions, such as sensing environmental conditions.

However, the complexity that can be achieved in such circuits has been limited by a critical bottleneck: the difficulty in assembling genetic components that don’t interfere with each other.

Unlike electronic circuits on a silicon chip, biological circuits inside a cell cannot be physically isolated from one another… Because all the cellular machinery …is jumbled together, researchers have to be careful that proteins that control one part of their synthetic circuit don’t hinder other parts of the circuit…

To expand the number of possible circuits, the researchers needed components that would not interfere with each other.  They started out by studying the bacterium that causes salmonella, which has a cellular pathway that controls the injection of proteins into human cells.

The pathway consists of three components: an activator, a promoter and a chaperone. A promoter is a region of DNA where proteins bind to initiate transcription of a gene. An activator is one such protein. Some activators also require a chaperone protein before they can bind to DNA to initiate transcription.

The researchers found 60 different versions of this pathway in other species of bacteria, and found that most of the proteins involved in each were different enough that they did not interfere with one another.

…there was a small amount of crosstalk between a few of the circuit components, so the researchers used an approach called directed evolution to reduce it. Directed evolution is a trial-and-error process that involves mutating a gene to create thousands of similar variants, then testing them for the desired trait. The best candidates are mutated and screened again, until the optimal gene is created.

…The researchers are now applying this work to create a sensor that will allow yeast in an industrial fermenter to monitor their own environment and adjust their output accordingly.

4-input AND gate (credit: Tae Seok Moon et al./Nature)

(via The most complex synthetic biology circuit yet | KurzweilAI)