Israeli researchers able to build enzymes ‘like Lego,’ in potential boon for drugs

Bold new technique at Weizmann Institute generates new enzymes with unprecedented scale, in possible boost to both chemical industry and development of medical treatments

Nathan Jeffay is The Times of Israel's health and science correspondent

An illustration showing four modular enzyme fragments (highlighted) that Weizmann Institute’s CADENZ method can combine to generate active enzymes at unprecedented scale. (Weizmann Institute of Science)
An illustration showing four modular enzyme fragments (highlighted) that Weizmann Institute’s CADENZ method can combine to generate active enzymes at unprecedented scale. (Weizmann Institute of Science)

Israeli scientists say they have developed a new method to construct enzymes “that’s like building Lego,” in the hope that they could eventually be used to engineer new drugs.

The discovery allows new enzymes to be created on such a rapid scale that the Weizmann Institute of Science team behind the research created a million enzymes in a single test tube — some 3,000 of which showed potential for development.

Enzymes are proteins that speed up chemical processes, like a fast-forward button on movies. Therefore the researchers behind the breakthrough say their work could “transform the chemical industry,” as well as advance medical developments.

By progressing the field of enzyme-building, the researchers hope to make it easier to safely break down pollutants, sewage and agricultural waste, and then turn them into biofuel or animal feed.

The study group, led by Prof. Sarel Fleishman of the Weizmann’s Biomolecular Sciences Department, published its findings on Thursday in the peer-reviewed journal “Science.”

Scientists have long been creating new enzymes, but Fleishman’s technique does so on unprecedented scale. “The standard approach in this field is to create hundreds of candidates to perform the function that is needed, screen them, and pick a ‘winner,’” Fleishman told The Times of Israel.

Weizmann Institute of Science researchers (left to right) Prof. Sarel Fleishman, Rosalie Lipsh-Sokolik and Dr. Olga Khersonsky. (Courtesy of the Weizmann Institute of Science)

“What we have done is to break down enzymes into fragments, with each fragment being a portion of a single protein. Then we can design new enzymes on computers in a modular way — by putting together fragments like building with Lego.”

An artificial intelligence technique developed in Fleishman’s lab is “learning” what function different combinations of fragments fulfill and determining which fragments should be pieced together to generate an enzyme that serves a particular purpose.

Scaling up the invention of new enzymes could provide a shortcut to inventing new drugs, Fleishman said. “In order to produce specific molecules for drugs, enzymes take source molecules and transform them chemically in to the substance that is desired for medical use,” he explained.

“The idea here is that you could optimize specific enzymes to get exactly the reactions you want, and widen the range of drugs we can make,” he added.

“Also, for existing drugs that are currently created not by enzymes but by polluting and inefficient processes, new enzymes could provide a significantly more environmentally friendly approach.”

The research got underway when Rosalie Lipsh-Sokolik, a PhD student in Fleishman’s lab, started experimenting with a family of several dozen enzymes that break down xylan, a common component of plant cell walls.

“If we manage to boost the activity of these enzymes, they might be used for breaking down plant compounds such as xylan and cellulose into sugars, which in turn can help generate biofuels,” Lipsh-Sokolik said. “Instead of disposing of agricultural waste, for example, we should be able to turn it into an energy source.”

Fleishman stated that the new Weizmann method, which he is calling CADENZ – short for Combinatorial Assembly and Design of Enzymes – produced more enzymes than could prove useful in one experiment than standard methods could produce in a decade.

“The first time we looked at the experimental results, we were amazed,” he said. “The sheer number of different active enzymes we got was staggering.”

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