Bacteria are nature's little workhorses, but their repertoire has its limits. Now, a Caltech team has bred bacteria that can make boron-carbon bonds, which were previously only possible in the lab. That new ability opens up the range of chemical compounds that bacteria could create, paving the way for easier and more environmentally-friendly production of drugs and other chemicals.
The researchers built on work from last year, where they engineered bacteria that were able to produce silicon-carbon compounds – another bond that's normally impossible in nature. They used a process called directed evolution, where enzymes are carefully evolved to serve a specific function. In this case, creating boron-carbon bonds.
"Nature has created beautiful machinery that we can benefit from," says Xiongyi Huang, co-lead author of the study. "We're repurposing nature's best inventions."
The researchers focused on cytochrome c, which is usually a common protein but in this case had a particular genetic variant. First, they mutated the gene that encodes that protein, then embedded the DNA into bacterial cells. When bacteria were successfully able to create boron-carbon bonds, their DNA was then further edited to improve that ability.
The researchers repeated this process over and over, making six different versions of the proteins and testing them in different bacterial cultures. Over time, they managed to refine their creations until they had bacteria that were up to 400 times more productive at making compounds containing boron-carbon bonds than the artificial techniques that are commonly used. Better yet, the researchers say the technique is very malleable, allowing them to make adjustments in future as needed.
"The protein DNA is like software that researchers can go in and rewrite," says Jennifer Kan, co-lead author of the study. "In traditional chemistry, you have to resynthesize a whole chemical catalyst if you want it to do something new. But we can do this by simply altering the DNA that tells the bacteria what to make."
Compounds containing boron-carbon bonds are used to make certain drugs and other products, and by enlisting bacteria to make them for us, the Caltech team says the process can be done at lower cost and with less damage to the environment.
"We have given life a whole new building block that it did not have before," says Frances Arnold, lead researcher on the project. "This is just the beginning. We've opened a new space for biology to explore, a space that includes useful products invented by humans."
The research was published in the journal Nature.
Source: Caltech