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'Unnatural' bugs to enhance our lives?

Salk Institute for Biological Studies

These bacterial smears show common E. coli strains that allow unnatural amino acid (Uaas) incorporation at one site only (left side), and an engineered strain that enables the incorporation of Uaas at multiple sites simultaneously (right side). The glow indicates the bacteria are producing full-length proteins with Uaas incorporated at different numbers of sites (as indicated by the surrounding numbers), a necessary step for their potential use in the production of new drugs and biofuels.

Scientists have successfully added multiple "unnatural" amino acids to a strain of bacteria, a breakthrough on the path to genetically engineered microbes that create useful things for people such as life-saving medicines and biofuels.

"We are adding components to the bug so that the bug can do something that a natural bug usually can't do," Lei Wang at the Salk Institute for Biological Studies told me today. "We are trying to make it do new tricks."


Amino acids are molecules built primarily from carbon, hydrogen, oxygen, and nitrogen. They assemble into various shapes and patterns to form the larger proteins. Proteins, in turn, carry out specific biological functions.

All life on Earth relies on a standard set of 20 amino acids. For years, researchers have genetically altered bacteria to perform certain tasks, such as produce the synthetic insulin diabetics use to regulate blood sugar levels. But until now, all such genetic engineering has relied on the 20 natural amino acids.

In the eyes of Wang, the world might be a better place if there were more building blocks available.

"If you can provide more building blocks, then you may be able to generate a new function for the proteins," he said. "And if you can create new functions for the proteins, then you may be able to synthesize new compounds using these proteins."

Examples of the potential compounds include drugs, industrial chemicals, and biofuels. 

Expanded genetic code
To do this, Wang's team created an essentially expanded genetic code for the bacteria, a strain of E. coli, with instructions to use multiple unnatural amino acids in the construction of proteins. 

The technology to put one unnatural amino acid at one place in the DNA has been around for about a decade, Wang said. The problem is that with just one position, "you cannot evolve anything, you cannot produce anything useful," he said. 

This limitation stemmed from that fact that bacteria produce another protein called release factor 1 (RF1) that stops the production of the protein containing the unnatural amino acid. To get around this, Wang's team removed RF1 and altered another protein, RF2, to keep the bug alive in the absence of RF1.

"We can now put unnatural amino acids at multiple places simultaneously and with very, very high efficiency … therefore you significantly increase your chance of generating new protein function and therefore generating new biosynthesis ability," he said. 

Complementary to 'synthetic life'
This approach to creating useful products with genetically enhanced bugs is complementary to efforts such as Craig Venter's well publicized effort to create synthetic lifeforms that could, potentially, produce biofuels, Wang said.

That effort, Wang explained, essentially attempts to reorganize and optimize the natural components of the genome to "make it better." The Salk team's effort gives the bug new building blocks. 

"They sort of help each other out," Wang said of the two approaches. "What they achieve can help us and what we helped achieve here can also help them."

Both approaches along with other efforts to genetically engineer microbes to produce useful products such as butanol may one day allow us to fill up our cars with fuel made by the genetically enhanced bugs or visit the pharmacy for a new class of drugs.

"We are not there yet, but that is exactly what we want to do in the next stage," Wang said.

More stories on engineered bacteria:


A paper on the findings appear in the Sept. 19 issue of the journal Nature Chemical Biology

John Roach is a contributing writer for msnbc.com.

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