Evolution is an incredible process that allows life to adapt to its environment. In 1990, Frances Arnold showed in her lab how we can use this process to our advantage by manipulating the evolution of microbes in a certain way. While this method earned Arnold the Nobel Prize in chemistry, his team is developing new antibiotics with this technique.
The team faced a challenge with their new antibiotics. Arnold’s team is developing a type of molecular ring, also known as a beta-lactam ring. These structures, which are essentially rings of atoms, disrupt the ability of bacteria to build a wall outside their cells, while effectively killing them. These structures have an important place in antibiotics such as penicillin.
Beta-lactam rings can be quite challenging to make. These structures first begin as a long chain of molecules and then bend backwards. Normally, chemists have to add extra guide molecules that tell them where to bend, and then remove them. This prolongs the process a little longer and increases the margin of error a little more.
Researchers began an attempt to streamline this process, unloading the hard work for enzymes. The team used the direct evolution technique to get the enzymes to evolve towards a certain path. The research team transferred the genetic codes of the enzymes into the bacteria so that these enzymes would be produced.
In this case, the team was able to evolve an enzyme called cytochrome P450, making it possible to produce beta-lactams. “We are developing new enzymes that cannot be found in nature,” said Inha Cho, co-author of the study. “Lactams can be found in many different drugs, especially antibiotics, but we always need a new one.”
These enzymes are among the most effective enzymes ever produced, and each capable of producing millions of beta-lactam molecules, the team said. These molecules are now available for industrial use, which is very positive news considering how quickly these bacteria have become resistant to antibiotics.