
Silkworms have had their genetic code hacked, allowing them to create a new kind of silk not found in nature. The hacking goes beyond the usual forms of genetic modification, by fundamentally altering the nature of the silk protein the animal makes. And unlike previous attempts at this, it will work on an industrial scale.
“The silkworm is the first ever industrially useful animal engineered to incorporate synthetic amino acids,” says Hidetoshi Teramoto of the in Japan, whose team carried out the work. A few other animals have been modified in similar ways, but only for research purposes.
Many groups are developing medical implants made of silk, such as scaffolds on which replacement organs could grow. The advantage of silk is that it doesn’t cause immune reactions when implanted in the body, and is already approved for medical use.
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What’s more, silk proteins can be turned into transparent films, sponges and even solid shapes. For instance, is testing a knee cartilage replacement made from silk protein.
But while the inertness of silk proteins is an advantage for replacing cartilage, it can be a problem for others, says of the University of Nottingham in the UK. For instance, it is hard for cells to attach themselves to silk.
There’s no easy solution, as chemically altering silk after it comes out of a silkworm does not work well, Thomas says. That’s partly because there’s no way to control exactly which parts of the protein get altered.
Silk hackers
So Teramoto and his team set out to create a silk protein with synthetic components that would act as anchor points for useful molecules – anything from growth factors to wash-proof dyes.
Every protein, including silk, is made of a chain of amino acids. To make a given protein, a cell strings the amino acids together in a particular order, which is encoded by a gene. All told there are 20 natural amino acids for the cell to use.
Teramoto’s team has genetically modified silkworms so that, when they are fed an artificial amino acid, they add it to the silk proteins they make.
Specifically, they have replaced one of the natural amino acids, phenylalanine, with an artificial one called AzPhe.
Altered enzymes
The method relies on hacking the silkworms’ cells. When a protein is being made, each of the 20 natural amino acids is carried into position by a molecule called transfer RNA (tRNA). Each amino acid has its own kind of tRNA, which the cell uses to ensure it has the right amino acid at each stage.
There is a particular enzyme that bolts phenylalanine onto its tRNA. Teramoto’s team tweaked this enzyme so that it instead adds AzPhe. Their first attempt, reported in 2014, didn’t work very well. The silkworms had to be fed lots of AzPhe, which is both expensive and bad for the animals ().
So the team has now evolved a version of the enzyme that is much better at recognising AzPhe. They did by generating thousands of gene variants, getting bacteria to make the enzymes and selecting the best . Then they put this in silkworms.
In these silkworms AzPhe replaces around 6 per cent of the phenylalanine in the silk protein when the caterpillars are fed just 0.05 per cent AzPhe by weight. That means the silk should not cost much more to produce than normal silk.
Wonder material
This doesn’t affect the desirable properties of the silk. “It’s still more silk than artificial,” says of the University of Sheffield in the UK.
What it does mean is that all kinds of molecules can then be easily added to the silk protein. The AzPhe amino acids enable something called “click chemistry”. “It’s basically a reliable reaction for attaching things,” says Thomas.
For instance, it could be used to attach dyes directly to silk. Normal silk does not hold on to dyes well and tends to bleed when washed. Alternatively, the silk could carry medicines.
Several other groups are pursuing similar approaches. In 2016, Thomas’ team used E. coli to make . They then attached an antibiotic to the silk proteins. The aim is to create smart dressings for wounds that don’t heal properly.
But E. coli can only produce mini-versions of a silk protein. And while everything from goats to potatoes have been engineered to produce silk proteins, we’ve yet to find a way to turn those proteins into fibres as strong as those spun by insects.
ACS Synthetic Biology