Nanotechnological Applications Based on Bacterial Encapsulins

Abstract

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.

Sequential, all-bioorthogonal reaction cascade catalyzed by a dual functional artificial metalloenzyme inside encapsulin

“…7 During the last years, activity of various (non-) natural guest enzymes inside these capsids was investigated. [8][9][10][11][12] Figure 1: The present research work is highlighted as a merging concept of several previously reported approaches. Moreover, future perspectives in ArM and nanoreactor research are shown.…”

“…The herein presented nanoreactor is the first report of a two-step, dual-functional ArM driven, fully bioorthogonal reaction cascade inside a proteinaceous capsid opening up exciting possibilities in the field of designing artificial organelles with compartmentalized reaction pathways. 8,9,[48][49][50] The novel gold-phosphine complex AuB is established herein for both bioorthogonal catalysis in aqueous solutions and as an avidin cofactor. With a TON above 400 its catalytic activity is comparable to the previously described gold-NHC complexes.…”

Exploring the Extreme Acid Tolerance of a Dynamic Protein Nanocage

“…Therefore, with future engineering applications in mind, we chose to focus our bioinformatic search for acid-tolerant shells on Family 1. 3,4,27,28 Further arguments for focusing on Family 1 are that the widespread DyP encapsulins found in Family 1 are known to optimally function under acidic conditions 29 while a variety of Family 1 systems encoded by acid-tolerant and acidophilic bacteria have already been previously identified. 4 As acid-tolerant proteins generally possess a low calculated isoelectric point (pI) caused by a large number of surface-exposed negatively charged residues, 22,25,26,30 it was hypothesized that encapsulins with a low pI may exhibit increased acid tolerance.…”

Recent advances in the structural biology of encapsulin bacterial nanocompartments

“…The in vitro structural and functional studies along with the in vivo work have been fruitful for understanding nanocompartment biology and this kind of work will continue to yield insights when applied to other nanocompartment complexes of unknown function. These studies will also lead to new insights into applications of bacterial nanocompartments in therapeutics and research ( Gabashvili et al, 2020 , Rodríguez et al, 2021 ).…”