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Researchers design protein that functions in cells as life-sustaining catalyst

Petri dish with growth of E. coli


Michael Hecht, a chemistry professor at Princeton University, and the researchers in his lab are designing and building proteins that can fold and mimic the chemical processes that sustain life. Hecht and his colleagues have confirmed that at least one of their new proteins can catalyze biological reactions in E. coli, meaning that a protein designed entirely from scratch functions in cells as a genuine enzyme. In this image, iron-rich medium supports the growth of E. coli engineered to no longer have a natural Fes enzyme. They form small, unhealthy, red colonies because they accumulate iron bound to enterobactin, and barely have enough free iron to grow. In contrast, cells containing the artificial enzyme Syn-F4 form large, healthy, white colonies because the novel protein catalyzes the cleavage of enterobactin and subsequent release of the iron needed for healthy growth. (Note: If these cells were placed on petri dishes with minimal iron, the red colonies would not appear at all because they would not have enough free iron to sustain cell growth.)

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Scientists in the field of articial biology are working toward creating a new organism.

In his lab at Princeton, chemistry professor Michael Hecht is working toward creating a genuinely new organism. Hecht and colleagues have confirmed that at least one of their new proteins can catalyze biological reactions, meaning that a protein designed entirely from scratch functions in cells as a genuine enzyme.

"Biology is the system of biochemical reactions and catalysts," says Hecht. "Each step has an enzyme that catalyzes it, because otherwise those reactions wouldn’t go fast enough for life to exist. … An enzyme is a protein that is a catalyst. They’re the best catalysts in the universe because evolution has spent billions of years selecting them. Enzymes can increase the speed of a reaction by many orders of magnitude."

After successfully creating artificial proteins for E. coli, Hecht and his team looked for critical functions that they could disrupt in these simple bacteria. They found four genes that, when removed, would not only render the E. coli inert -- effectively dead -- but which their artificial proteins could then "rescue," or resuscitate.

First identified by Hecht in 2011, the researchers have spent the past six years working to determine the precise mechanisms by which their new proteins functioned.

This research was funded in part by the National Science Foundatoin (NSF) (grant MCB 14-09402).

Read more about this research in the NSF News From the Field story Protein designed entirely from scratch functions in cells as a genuine enzyme. (Date image taken: 2015; date originally posted to NSF Multimedia Gallery: June 20, 2018)

Credit: Ann Donnelly, Hecht Lab, Princeton University

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