A team of researchers from Caltech has bioengineered bacteria that can produce compounds with boron-carbon bonds. Until now, this ability of “borylation” had been restricted to only laboratory chemists.
As described in their publication in Nature, the team applied directed evolution on E. coli that express a variant cytochrome c enzyme. This variant was derived from Rhodothermus marinus, a bacterium that normally thrives in Icelandic hot springs. To direct the evolution of the enzyme, the team mutated the encoding gene and introduced it into thousands of recombinant bacteria in search of mutants that can create the desired boron-carbon bonds. Resulting mutant enzymes with the desired function were then further mutated until the bacteria became highly proficient at synthesizing the boron-carbon compounds.
This method of synthetically evolving enzymes was pioneered in the 1990s by Frances Arnold himself, the principal investigator of the study. "We have given life a whole new building block that it did not have before," says Arnold. "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 team generated six versions of the cytochrome c, each with slightly different affinities for making boron-carbon compounds—up to 16 different organoboranes. Bacteria containing this enzyme have even shown efficiencies up to 400 times greater than those of existing methods to chemically synthesize such compounds.
Elemental boron sits just to the left of carbon on the periodic table. It is commonly found in industrial materials and fertilizers, and is an essential nutrient for plants. NASA's Curiosity rover has even documented its presence on Mars. Some pharmaceutical agents incorporating boron include boric acid (antiseptic), Bortezomib (antitumor proteasome inhibitor), and Tavaborole (antifungal).
"Boron is one of chemistry's unsung heroes. It is not an element we hear about every day, but its contribution to chemistry is tremendous,” says study first author Jennifer Kan. “We are excited to add this element to the synthetic biology toolbox for the first time."
Image: An artist's interpretation of a scientist introducing boron to the carbon-based chemistry of life. Image courtesy of David Chen and Yan Liang (BeautyOfScience.com) for Caltech.