Protein-building nanomachines
Sarah Byrne investigates an alternative to boring and long chemical synthesis
Inside every cell, tiny biological machines are hard at work, constructing the proteins that will perform vital roles as enzymes, hormones, and a wide variety of other structural and biochemical functions. These molecular machines, called ribosomes, translate our genetic code into a protein sequence, and assemble the amino-acid building blocks into the peptide chain that folds into a functional protein.
Researchers led by Dave Leigh at Manchester University have recently developed an artificial nanoscale machine that can perform a similar function. This consists of a ring-shaped molecule called a rotaxane, which moves along an axle on which amino acids have been loaded. A ‘reactive arm’ then sequentially picks off each amino acid and adds it to a chain attached to the rotaxane itself, forming a new peptide molecule. Rotaxane nanomachines have been developed before, but never one that can perform sequential actions like this. In results published in Science this month, a peptide was successfully synthesised in milligram quantities – a significant amount and useful for analysis – with an incredible 1018 of the nanobots working in parallel.
However, the synthetic ‘ribosome’ cannot yet do everything a real one can. It cannot, for example, read the genetic code and determine which order the amino acids should be assembled in – these need to be pre-loaded onto the molecular axle. It is also extremely slow compared to the real ribosome, taking hours rather than milliseconds to attach each new amino acid.
There also may be some questions to be asked about the usefulness of the approach in general: whether trying to mimic the way nature does things is necessarily the best way. Nature is by definition messy and at times overly complex: biological systems tend to come with a lot of baggage from their evolutionary history, and the randomness inherent in their development. If, for example, you want to synthesise peptide chains, we already have much simpler and more efficient ways of doing that in the lab, using standard biochemical techniques.
Curiously though, Prof. Leigh seems to hope that beyond being a fascinating proof-of-concept, the synthetic ribosome will someday prove a more effective means of synthesising peptides than the current ‘laborious’ process of chemical synthesis. This is perhaps not as unlikely as it sounds: researchers have developed synthetic enzymes that are simpler and more efficient than the natural versions. It is often entirely possible to improve on nature, and with the new results emerging from the Leigh lab and the synthetic biology field in general, there are sure to be interesting developments to come.
