Nanoreactor Design Based on Self-Assembling Protein Nanocages

Abstract

Self-assembling proteins that form diverse architectures are widely used in material science and nanobiotechnology. One class belongs to protein nanocages, which are compartments with nanosized internal spaces. Because of the precise nanoscale structures, proteinaceous compartments are ideal materials for use as general platforms to create distinct microenvironments within confined cellular environments. This spatial organization strategy brings several advantages including the protection of catalyst cargo, faster turnover rates, and avoiding side reactions. Inspired by diverse molecular machines in nature, bioengineers have developed a variety of self-assembling supramolecular protein cages for use as biosynthetic nanoreactors that mimic natural systems. In this mini-review, we summarize current progress and ongoing efforts creating self-assembling protein based nanoreactors and their use in biocatalysis and synthetic biology. We also highlight the prospects for future research on these versatile nanomaterials.

Self‐Assembly in Protein‐Based Bionanomaterials

“…In addition, many similar non-native artificial structures having specific structures have been modelled and investigated in silico (Figure 1). [37,65,66] In recent years, both "top-down" and "bottom-up" approaches have been utilized in constructing nano-reactors for biocatalysis and synthetic biology. [67][68][69] Several proteinaceous microcompartments were engineered to load exogenous biocatalysts and have been successfully constructed in wellstudied hosts like E. coli.…”

“…Examples of natural and non-natural proteinaceous compartments. Reprinted from Ref [65]. Published by MDPI.…”

Synthetic Biology for Multiscale Designed Biomimetic Assemblies: From Designed Self-Assembling Biopolymers to Bacterial Bioprinting

“…One promising example in this area is nanocages: protein assemblies that show a great potential to be developed into artificial stimuli-responsive or programmable bionanomachines functioning as drug/gene carriers, biosensors, imaging agents, vaccine/immuno modulators, or nanoreactors for biocatalysis. 105 Currently, clinical applications of self-assembled protein nanocages are still limited, 106 but further engineering and introduction of responsiveness to molecular or environmental signals will bring solutions for the enhancement of their targeting capacity or penetration efficiency. We can also expect new abilities for nanocages to modulate the immune response and to feature enhanced biocompatibility and biodegradability via engineering of external cage surfaces.…”

Two-tier supramolecular encapsulation of small molecules in a protein cage

“…Among biomolecular compartments, protein-based containers are attractive owing to their welldefined structures, diverse functionalities, and genetic manipulability 4 . Natural and artificial protein cages are ideal hosts for macromolecules, a property that has been exploited to produce a wealth of engineered nanosystems [5][6][7][8][9][10][11] , from catalytic compartments 12,13 to virus mimics 14 . Critical to the success of these designs has been predictable molecular recognition between components.…”