Lumazine

Naturally occurring and computationally ab initio designed protein cages can now be considered as extremely suitable materials for new developments in nanotechnology. Via self-assembly from single identical or non-identical protomers large oligomeric particles can be formed. Virus-like particles have today found a number of quite successful applications in the development of new vaccines. Complex chimeric nanoparticles can serve as suitable platforms for the presentation of natural or designed antigens to the immune system of the host. The scaffolds can be cage forming highly symmetric biological macromolecules like lumazine synthase or symmetric self-assembling virus-like particles generated by computational ab initio design. Symmetric nanoparticle carriers display a structurally ordered array of immunogens. This feature can lead to a more favorable interaction with B-cell receptors, in comparison to the administration of single recombinant immunogens. Several pre-clinical animal studies and clinical studies have recently pointed out the efficiency of nanoparticle antigens produced recombinantly in creating strong immune responses against infectious diseases like HIV, Malaria, Borrelia, Influenza.

Nanoscale compartments formed by hierarchical protein self-assembly are valuable platforms for nanotechnology development. The well-defined structure and broad chemical functionality of protein cages, as well as their amenability to genetic and chemical modification, have enabled their repurposing for diverse applications. In this review, we summarize progress in the engineering of the cage-forming enzyme lumazine synthase. This bacterial nanocompartment has proven to be a malleable scaffold. The natural protein has been diversified to afford a family of unique proteinaceous capsules that have been modified, evolved and assembled with other components to produce nanoreactors, artificial organelles, delivery vehicles and virus mimics.

Lumazine synthase (LS) is a family of enzyme involved in the penultimate step in the biosynthesis of riboflavin. Its enzymatic mechanism has been well defined, and many LS structures have been solved using X-ray crystallography or cryoelectron microscopy. LS is composed of homooligomers, which vary in size and subunit number, including pentamers, decamers, and icosahedral sixty-mers, depending on its species of origin. Research on LS has expanded beyond the initial focus on its enzymatic function to properties related to its oligomeric structure and exceptional conformational stability. These attributes of LS systems have now been repurposed for use in various biomedical fields. This review primarily focuses on the applications of LS as a flexible vaccine presentation system. Presentation of antigens on the surface of LS results in a high local concentration of antigens displayed in an ordered array. Such repetitive structures enable the cross-linking of B-cell receptors and result in strong immune responses through an avidity effect. Potential issues with the use of this system and corresponding solutions are also discussed with the objective of improved utilization of the LS system in vaccine development.