Washington: Researchers have discovered an unexpected way in which a synthetic protein promotes the growth of cells that lack the natural gene, offering insight into how life can adapt to survive and potentially be reinvented.
Researchers from Princeton University in US discovered the unexpected way in which a 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.
Researchers first discovered SynSerB's ability to rescue serine-depleted E coli 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.
"These are novel proteins that have never existed on Earth, and are not related to anything on Earth yet they enable life to grow where it otherwise would not," said Michael Hecht from Princeton University.
Natural proteins are complex molecular machines constructed from a pool of 20 different amino acids. Typically they range from several dozen to several hundred amino acids in length.
Researchers developed a library of non-natural proteins guided by a concept called binary design. The idea was to narrow down the number of possible sequences by choosing from eleven select amino acids that were divided into two groups - polar and non-polar.
By using only the polar or non-polar characteristics of those amino acids, researchers could design a plethora of novel proteins to fold into a particular shape based on their affinity to and repulsion from water.
Then, by allowing the specific positions to have different amino acids, researchers were able to produce a diverse library of about one million proteins, each 102 amino acids long.
"We had to focus on certain subsets of proteins that we knew would fold and search there first for function," said Katie Digianantonio from Princeton University.
Having found several non-natural proteins that could rescue specific cell lines, this latest work details researchers' investigation specifically into how SynSerB
promotes cell growth.
To discern SynSerB's mechanism among the multitude of complex biochemical pathways 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 showed that SynSerB 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, researchers said.
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, they said.
The findings were published in the journal Proceedings of the National Academy of Sciences.
