Allocating resources to synthetic circuits in bacteria may help drug production

Allocating resources to synthetic circuits in bacteria may help drug production

Bacteria could be programmed to efficiently produce drugs, thanks to breakthrough research into synthetic biology using engineering principles.

New research has discovered how to dynamically manage the allocation of essential resources inside engineered cells - advancing the potential of synthetically programming cells to combat disease and produce new drugs.

The researchers have developed a way to efficiently control the distribution of ribosomes - microscopic 'factories' inside cells that build proteins that keep the cell alive and functional - to both the synthetic circuit and the host cell.

Synthetic circuitry can be added to cells to enhance them and make them perform bespoke functions - providing vast new possibilities for the future of healthcare and pharmaceuticals, including the potential for cells specially programmed to produce novel antibiotics and other useful compounds.

A cell only has a finite amount of ribosomes, and the synthetic circuit and host cell in which the circuitry is inserted both compete for this limited pool of resources. It is essential that there are enough ribosomes for both, so they can survive, multiply and thrive. Without enough ribosomes, either the circuit will fail, or the cell will die - or both.

Using the engineering principal of a feedback control loop, commonly used in aircraft flight control systems, the researchers have developed and demonstrated a unique system through which ribosomes can be distributed dynamically - therefore, when the synthetic circuit requires more ribosomes to function properly, more will be allocated to it, and less allocated to the host cell, and vice versa.

By expressing a synthetic 16S rRNA with altered specificity, authors could partition the ribosome pool into host-specific and circuit-specific activities. They show mathematically and experimentally that the effects of resource competition can be alleviated by targeting genes to different ribosomal pools. This division of labour can be used to increase flux through a metabolic pathway.

Auhtors develop a model of cell physiology which is able to capture these observations and use it to design a dynamic resource allocation controller.

Ribosomes live inside cells, and construct proteins when required for a cellular function. When a cell needs protein, the nucleus creates mRNA, which is sent to the ribosomes - which then synthesise the essential proteins by bonding the correct amino acids together in a chain.