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Scientists deploy directed evolution to create new antibiotics

By Brooks Hays
Scientists likened the creation of a lactam ring, the looping of a molecular chain onto itself, to tying one end of a string to its middle. Photo by Caltech
Scientists likened the creation of a lactam ring, the looping of a molecular chain onto itself, to tying one end of a string to its middle. Photo by Caltech

May 10 (UPI) -- Scientists have developed a better way to build new antibiotics.

Using a method known as directed evolution, researchers successfully synthesized beta-lactams, a molecular structure used to create antibiotics.

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Most antibiotics, including the most famous antibiotic, penicillin, are anchored by beta-lactams. Traditionally, scientists create beta-lactams by taking a chain-like molecule and affixing one end of the chain to its middle, forming a loop.

Usually, scientists are forced to patch extra pieces onto molecules to build beta-lactams. Without the extra components, the resulting beta-lactams tend to be inconsistent in size. Some get tied too short, others tied too long -- forming an undesirable mix of small and large loops.

Adding on extra pieces promotes consistency, but it also adds complexity to the synthesizing process.

Scientists found a better way to create beta-lactams using directed evolution. In the lab, scientists produced enzymes. Researchers allowed the enzymes to evolve until they behaved as desired. Then, scientists took the genetic code of the most useful enzymes and transplanted it into the genome of bacteria. As bacteria reproduce, they replicate the useful enzyme.

For the latest tests, scientists evolved the enzyme known as cytochrome P450 to produce beta-lactams. Researchers also evolved two other enzymes to produce different sized lactams, a gamma-lactam and delta-lactam, which are different-sized loops featuring different combinations of nitrogen and carbon atoms.

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Researchers expect their new synthesis method -- detailed this week in the journal Science -- to simplify the process of designing new antibiotics.

"We're developing new enzymes with activity that cannot be found in nature," Inha Cho, a graduate student at California Institute of Technology, said in a news release. "Lactams can be found in many different drugs, but especially in antibiotics, and we're always needing new ones."

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