The Biomaterials Problem
Biomaterials have the ability to replace animal leather, plastic and textiles whilst simultaneously leaving a smaller carbon footprint. Synthetic silk, collagen, elastin and keratin are biomaterials which are commonly referred to when discussing replacements to our current harmful chemical polymers. The biomaterials manufacturing industry is in need of a modular platform capable of polymerising and functionalizing these proteins. This would enable the manufacturers to create tunable materials with varying properties.
The Theoretical Solution
A tunable platform in biomaterials means proteins of different properties can be fused together in a reliable manner. Ideally, steric hindrance would be negligible when fusing proteins. Furthermore, you should be able to control the amount of polymerisation and how long polymers are. Polymer length is a key parameter to enabling tunable properties as this will impact on their behaviour.
The Intein Miracle
Since Anraku and Stevens discovered intein proteins in 1990, protein engineering has had a powerful control element added to their toolbox. Inteins enable proteins of choice to fuse together simultaneously leaving behind an insignificant scar. The size of this amino acid scar means steric hindrance is minimal and does not impede on natural protein folding. Split inteins are synthesised individually and when they come in close contact they will fuse N- and C- termini and excise out the exteins. This enables two biomaterial proteins to be fused together.
Modular and Orthogonal
SETA is taking intein polymers one step further by creating a modular platform for polymerization and functionalization of proteins. Fixed restriction sites create a plug-and-play tool for inserting biomaterial proteins in between inteins. The modular platform consists of two orthogonal intein flanked monomers and an intein passenger for capping. The intein monomer tool enables endless polymerisation by fusing biomaterial proteins to each other whilst the intein passenger stops this process by fusing a functional protein with no flanking inteins.
A Spider Silk Model
Spider silk gained fame thanks to its mechanical properties rendering it stronger than steel. The protein biopolymer is also biodegradable and biocompatible making it an ideal substitute to undegradable chemical polymers like plastics. Given the novelty value amongst the public, the abundance of literature and the presence of growing industry, we decided to model SETA on spider silk polymerisation and functionalization.
