Researchers at the John Innes Centre (JIC) in Norwich, UK, have been studying a "nanomachine" in soil bacteria called the twin-arginine translocation (Tat) system, which the bacteria use to secrete a range of proteins that help them digest food and compete with other microorganisms in the soil. They found that this nanomachine was used to produce a greater variety of proteins than they previously thought, including proteins with lipid anchors and large proteins.

The biotechnology industry already uses bacteria to make proteins to use in biopharmaceuticals, but some are difficult to produce using current methods, mainly because the proteins are secreted unfolded.

Indeed, for a long time, the researchers have known that bacteria secrete proteins unfolded through the membrane and then fold it up into the right shape.

But they discovered that the Tat system folds the proteins first and then exports them - a finding that could have a huge potential for protein production in bacterial species that are already used for this purpose - including Bacillus and Escherichia coli.

"Currently, the proteins used by the biopharmaceutical industry are secreted by bacteria's general secretion pathway (GSP) which transports unfolded proteins," Tracy Palmer, molecular biologist at the JIC and leader of the team, told In-PharmaTechnologist.com.

"But this method doesn't have a good capacity and allows the production of only a handful of proteins."

By harnessing the Tat system, the scientists hope that it will represent a significant alternative and it will then be easier to make these proteins for biotechnological and biomedical purposes, a market predicted to reach $2.6bn (€2bn) this year, an increase from $1.4bn in 2003, according to Research and Markets.

Bacterial protein secretion is a fundamental biological process that can be exploited to the benefit of human health through the biotechnological production of biopharmaceuticals. On the other hand, secreted bacterial toxins and virulence factors represent a major threat to human health.

In practice, the Tat nanomachine selects which proteins to secrete by recognising a short signal sequence attached to the end of the protein.

"Our collaborators at the University of Pennsylvania have developed a computer program to search the bacterial genome to predict which proteins use the Tat system, and in this study we have verified their results experimentally and found a significant number of signals that are recognised by this system," said Palmer.

She added that the next step is to attach these signals to medically important proteins so they can be secreted by the bacteria using the Tat system.

Palmer's team has recently joined forces with the "Tat Machine Project", an EU-funded consortium of researchers from across Europe studying the Tat system.

In addition to using the Tat nanomachine to improve production of biopharmaceuticals, the consortium are studying the system in several different types of bacteria, including pathogenic species like E. coli O157 and Pseudomonas aeruginosa to explore Tat as a potential target for new antibiotics.

The research was published in Proceedings of the National Academy of Sciences (PNAS) journal on 7th November.