Scientists Engineer Bacteria That Create Energy-Packed Rings

Bacterial enzymes bred in a Caltech laboratory can produce high-energy carbon rings rarely found in nature. These molecular structures can then be used in the creation of other material.
Loukia Papadopoulos

Caltech scientists have engineered bacteria that can make tiny yet energy-packed carbon structures that serve as starting points for the creation of other material. These difficult-to-engineer molecular structures in the shape of rings can now be "brewed" similarly to beer.

Directed evolution used to mimic nature

The bacterial enzymes were bred in the lab of Caltech's Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry Frances Arnold. To do this, Arnold’s researchers used a technique she developed in the 1990s called directed evolution.

The technique enables scientists to breed bacteria with traits that they desire and that are rarely or not at all found in nature. In previous tests, Arnold's lab used the technique to produce bacteria that create carbon-silicon and carbon-boron bonds, bonds that were previously only man-made.

"Bacteria can now churn out these versatile, energy-rich organic structures," Arnold said. "With new lab-evolved enzymes, the microbes make precisely configured strained rings that chemists struggle to make."

The research was published in a paper entitled "Enzymatic Construction of Highly Strained Carbocycles" in the April 5 issue of Science. The paper describes how the researchers coaxed Escherichia coli bacteria into creating bicyclobutanes.

According to Caltech, unlike other carbon rings, bicyclobutanes are not common in nature likely due to their “inherent instability or the lack of suitable biological machineries for their assembly.” Arnold’s lab, however, has now shown that “bacteria can be genetically reprogrammed to produce bicyclobutanes from simple commercial starting materials”.

A new pathway for bacteria is introduced

"To our surprise, the enzymes can be engineered to efficiently make such crazy carbon rings under ambient conditions," said graduate student Kai Chen, lead author on the paper. "This is the first time anyone has introduced a non-native pathway for bacteria to forge these high-energy structures." 

Caltech reported that Chen and his team “did this by giving the bacteria a copy of a gene that encodes an enzyme called cytochrome P450. The enzyme had previously been modified through directed evolution by the Arnold lab and others to create molecules containing small rings of three carbon atoms—essentially half of a bicyclobutane group.”


Postdoc and member of Arnold's lab Xiongyi Huang said: "The beauty is that a well-defined active-site environment was crafted in the enzyme to greatly facilitate the formation of these high-energy molecules." 

Postdoc and member of Arnold’s lab Jennifer Kan added that advancements like this could push chemistry in a “greener direction”. "In the future, instead of building chemical plants for making the products we need to improve lives, wouldn't it be great if we could just program bacteria to make what we want?" she said.

The research was funded by the National Science Foundation, the National Institutes of Health, and the Donna and Benjamin M. Rosen Bioengineering Center.