University of Oxford researchers Mark Howarth, Bijan Zakeri, and others have developed a super-strength molecular glue by engineering an unusual protein from a type of bacteria that can cause life-threatening disease--the flesh-eating bacteria Streptococcus pyogenes. The bacterium uses the protein FbaB to help invade human cells. The researchers genetically split a domain of FbaB into two parts--a small peptide component and a larger protein component. Thus, rather than the amide bond formation occurring within the protein, amide bond formation could serve to lock two separate molecules together. Abbreviating Streptococcus pyogenes to Spy, they termed the peptide 'SpyTag' and the protein partner 'SpyCatcher'. They found that SpyTag docked with SpyCatcher and then rapidly formed an amide bond, thereby locking the two partners together. Both SpyTag and SpyCatcher are composed of the usual 20 amino acids common to all organisms. Therefore, they can be genetically fused to any protein of interest and expressed in different organisms.
Because of its high tolerance to acidity, alkalinity, high and low temperatures, detergents, and other conditons, SpyTag can be used with the addition of artificial amino acids or cofactors. This makes it more life-friendly for medical uses. In addition, SpyTag and SpyCatcher form a covalent bond with high specificity at the surface of human cells, which results in them reacting with each other, but not the many other proteins present.Source: Zakeri B; Fierer JO; Celik E; Chittock EC; Schwarz-Linek U; Moy VT; Howarth M. 2012. Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin. Author Summary. PNAS: 109(12):4347-4348.
This process is mimicking a natural chemical process, and the process gives rise to a variety of compounds. But to make the process work, it looks like they genetically engineer bacteria to do the chemistry. Therefore, in a strict sense, it's not biomimicry, but a step in the right direction.
Many protein-catalyzed reactions are highly sensitive to their conditions, occurring only within a narrow range of pH values and temperatures and requiring particular cofactors or metal ions. The SpyTag reaction works is a wide variety of conditions.Edit Summary