New research in synthetic biology has demonstrated that bacteria can be manipulated to produce drugs efficiently using an engineered circuit inside the cell that shares the host cell’s protein-producing machinery. The research team showed mathematically and then experimentally a method that allows the host cell and artificial circuit to successfully share the limited number of ribosomes inside the cell. The paper describing the research is published in Nature Communications.
Ribosomes are highly complex pieces of cellular machinery responsible for translating RNA into protein. A cell with a synthetic circuit requires extra ribosomal resources to meet the translation needs of the host and have adequate protein production power needed for the circuit to function effectively. By introducing orthogonal ribosomes (o-ribosomes), specialized ribosomes that can selectively translate mRNA not recognized by the host ribosome, the team was able to segment the ribosome pool into host-specific and circuit-specific activities inside the cell. A feedback controller was used to dynamically distribute ribosomal resources to the host and circuit. The controller increased o-ribosome production when demand for translational resources by the circuit increased.
"Synthetic Biology is about making cells easier to engineer so that we can address many of the most important challenges facing us today - from manufacturing new drugs and therapies to finding new biofuels and materials. It's been hugely exciting in this project to see an engineering idea, developed on a computer, being built in a lab and working inside a living cell,” comments Declan Bates, Professor of Bioengineering at the University of Warwick's School of Engineering and Co-Director, Warwick Integrative Synthetic Biology Centre (WISB).
This important study emphasizes that synthetic biology techniques could be used to efficiently produce antibiotics and other drugs more efficiently than current methods.