Reviving dying cells with artificial protein

Offering new insight into how life can adapt to survive and potentially be reinvented, researchers have discovered how a synthetic protein promotes the growth of cells that lack a life-sustaining gene.

"These are novel proteins that have never existed on Earth, and aren't related to anything on Earth yet they enable life to grow where it otherwise would not," said corresponding author Michael Hecht, professor of chemistry at Princeton University in the US.

The findings, published in the journal Proceedings of the National Academy of Sciences, showed how the synthetic protein called SynSerB promotes the growth of cells that lack the natural SerB gene, which encodes an enzyme responsible for the last step in the production of the essential amino acid serine.

The Hecht group first discovered SynSerB's ability to rescue serine-depleted E. coli bacteria cells in 2011. At that time, they also discovered several other de novo proteins capable of rescuing the deletions of three other essential proteins in E. coli.

Having found several non-natural proteins that could rescue specific cell lines, this latest work details their investigation specifically into how SynSerB promotes cell growth.

The most obvious explanation, that SynSerB simply catalysed the same reaction performed by the deleted SerB gene, was discounted by an early experiment.

To discern SynSerB's mechanism among the multitude of complex biochemical mechanisms in the cell, the researchers turned to a technique called RNA sequencing.

This technique allowed them to take a detailed snapshot of the serine-depleted E. Coli cells with and without their synthetic protein and compare the differences.

The RNA sequencing experiment revealed that the artificial protein induced overexpression of a protein called HisB, high levels of which have been shown to promote the key reaction normally performed by the missing gene.

By enlisting the help of HisB, the non-natural protein was able to induce the production of serine, which ultimately allowed the cell to survive, the researchers said.