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Encapsulins are proteinaceous nanocontainers, constructed by a single species of shell protein that self-assemble into 20-40 nm icosahedral particles. Encapsulins are structurally similar to the capsids of viruses of the HK97-like lineage, to which they are evolutionarily related. Nearly all these nanocontainers encase a single oligomeric protein that defines the physiological role of the complex, although a few encapsulate several activities within a single particle. Encapsulins are abundant in bacteria and archaea, in which they participate in regulation of oxidative stress, detoxification, and homeostasis of key chemical elements. These nanocontainers are physically robust, contain numerous pores that permit metabolite flux through the shell, and are very tolerant of genetic manipulation. There are natural mechanisms for efficient functionalization of the outer and inner shell surfaces, and for the in vivo and in vitro internalization of heterologous proteins. These characteristics render encapsulin an excellent platform for the development of biotechnological applications. Here we provide an overview of current knowledge of encapsulin systems, summarize the remarkable toolbox developed by researchers in this field, and discuss recent advances in the biomedical and bioengineering applications of encapsulins.
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http://dx.doi.org/10.3390/nano11061467 | DOI Listing |
Mater Adv
July 2025
Department of Biological Chemistry, University of Michigan Ann Arbor MI 48109 USA
Encapsulins are a widely distributed and functionally diverse class of protein compartments found across diverse bacterial and archaeal phyla involved in various aspects of microbial metabolism. They self-assemble into cargo-loaded protein shells between 20 and 50 nm in diameter with either = 1, = 3 or = 4 icosahedral symmetry. Encapsulin nanocages possess several key features that make them an attractive engineering platform for creating nanocarrier-based drug delivery systems.
View Article and Find Full Text PDFCurr Opin Microbiol
August 2025
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Internal cellular organization is a defining feature of life, and encapsulins are an effective, protein-based method for prokaryotic cells to achieve compartmentalization of chemical reactions and metabolic processes. The defining feature of encapsulins is their ability to encapsulate cargo proteins inside a self-assembling protein shell, mediated by cargo-encoded targeting peptides or domains. The biochemical and physiological function of an encapsulin system is dictated by the catalytic activity of encapsulated components, with the protein shell acting as a selectively permeable diffusion barrier.
View Article and Find Full Text PDFInt J Biol Macromol
August 2025
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, CDMX 04510, Mexico. Electronic address:
Oxidative therapy for cancer treatment represents a promising application of nanoreactors in medicine, but there is still a lack of systems to deliver the oxidative enzymes to target tissues. Encapsulins, a novel class of nanocompartments found in bacteria and archaea, can encapsulate specific enzymes, offering significant potential for developing nanoreactors. This study explored the development of a nanoreactor based on the bacterial enzyme pyridoxine 4-oxidase (PNOX).
View Article and Find Full Text PDFACS Biomater Sci Eng
July 2025
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
African swine fever (ASF) represents a significant threat to the global swine industry due to the absence of a commercially available vaccine. The rational design of vaccine antigens is crucial for improving vaccine efficacy and guiding its development. The p30 protein of the African swine fever virus (ASFV) is an early membrane protein involved in the viral invasion of host cells.
View Article and Find Full Text PDFAdv Sci (Weinh)
August 2025
Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
Protein shells or capsids are a widespread form of compartmentalization in nature. Viruses use protein capsids to protect and transport their genomes while many cellular organisms use protein shells for varied metabolic purposes. These protein-based compartments often exhibit icosahedral symmetry and consist of a small number of structural components with defined roles.
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