Synthetic genes can make weird new proteins that actually work

These never-before-seen artificial proteins replaced natural ones in living cells

Original source: New Scientist

Artificial proteins, created from scratch with no particular design in mind, can do the work of a natural protein. The discovery may widen the toolkit of synthetic biologists trying to build bespoke organisms.

There are more proteins possible than there are atoms in the universe, and yet evolution has tested only a tiny fraction. No one knows whether the vast, untried space of proteins includes some that could have biological uses.

Until now, most researchers assembling novel proteins have meticulously selected each amino acid building block so that the resulting protein folds precisely into a pre-planned shape that closely fits the molecule it is intended to interact with. Michael Hecht, a chemist at Princeton University, decided to try a much looser approach. “I was trying to see what the hell’s out there,” he says.

He generated a million different proteins and then inserted the genes coding for them into E. coli bacteria that had other genes deleted (and hence, the proteins they coded for). The missing genes coded for proteins that catalyse biochemical reactions.

For four of the 80 gene deletions Hecht worked on, at least one – and in one case, hundreds – of the semi-random novel proteins restored the missing function. “We were ecstatic,” says Hecht.

They somehow “upregulated” other, related proteins in the bacteria so that they could take over for the absent ones, he recently told the Astrobiology Science Conference in Mesa, Arizona. The team hope this approach will eventually lead to a wide range of novel proteins.

“These never-before-seen artificial proteins replaced natural ones in living cells – we were ecstatic”

So far, Hecht can’t predict the function of his novel proteins, says Nicholas Hud at the Georgia Institute of Technology. That means a huge amount of trial and error is needed to find something useful. “De novo design of enzymes is still a bit beyond our reach,” says Hud.