CREDIT LINE42 THE SCIENTIST | the-scientist.com
CREDIT LINEPRACTICAL APPLICATIONS
What researchers discover about bacterial nano- and microcompartments could be of use to bioengineers, who are eyeing the structures for
their own purposes. Each compartment has its advantages. Encapsulin nanocompartments, for instance, are simple systems in which the cargo
enzymes co-assemble with highly stable shells. Larger microcompartment types are more complex and less stable, but they have a size advantage,
allowing them to hold more cargo. Researchers ought to be able to play with their structures, altering pore size and cargoes, to create compartments
for specific purposes, says Martin Warren, a biochemist at the University of Kent in Canterbury, England.
As a proof of principle, Warren’s group altered propanediol-metabolizing microcompartments, which normally package three enzymes in that
pathway, to fill them with two new enzymes, a pyruvate decarboxylase and an alcohol dehydrogenase. The resulting bioreactor efficiently trans-
formed pyruvate, the product of glycolysis, into ethanol (ACS Synth Biol, 3:454–65, 2014). Now, Warren is collaborating with companies to produce
high-value chemicals such as biofuels. Other potential applications include fixing nitrogen, to make a microcompartment-based fertilizer, or
carbon, perhaps to engineer plants that are super efficient at fixing carbon. Another thought is to use microcompartments in waste cleanup.
In medicine, one might engineer desirable gut bacteria to use microcompartments so that pathogens that contain them, such as Sal-
monella, would lose their edge, speculates Cheryl Kerfeld of Michigan State University and the Lawrence Berkeley National Laboratory.
Alternatively, researchers could design antibiotics that target pathogenic bacteria’s microcompartments, leaving commensals unharmed,
posits Danielle Tullman-Ercek, a chemical engineer at Northwestern University. Others suggest that with their polyhedral, often virus-
like shape, nano- and microcompartments sporting pathogen-specific antigens would make ideal vaccines. Or, offers Warren, microcom-
partments might be good drug-delivery vehicles.
Gil Westmeyer, a physician and bioengineer at Technical University Munich, hopes to use nanocompartments as imaging probes within mam-
malian cells. In a recent study, his group engineered human kidney cells to express nanocompartments similar to those found in Myxococcus xan-
thus, and altered the interior components to produce contrast agents for various imaging platforms (Nat Commun, 9:1990, 2018). To use these,
researchers might force production of nanocompartments only in certain cell types, or engineer the compartments’ exteriors to target them to
specific cellular structures, says Westmeyer, adding that “there will be applications that we cannot even imagine right now.”
So far, no synthetic nano- or microcompartment applications have been commercially realized. “We need to actually show that these things
have a use,” Warren says.
To speed the engineering of microcompartments, Kerfeld recently developed an artificial system to load the protein shells with cargo. Researchers
in her lab used a standard protein-linking system made up of two peptides, SpyTag and SpyCatcher, that bond when they meet. The scientists
hooked one half of the duo to the interior of the shell, and the other half to the desired cargo proteins, effectively controlling what ended up inside.
In addition, they tagged the shells for affinity purification (Nat Commun, 9:2881, 2018).
These tools will significantly accelerate research and bioengineering, says Tullman-Ercek. “There are so many applications for these little guys.”an iron-storage protein that potentially protected the cells from
oxidative stress.^1
McHugh and colleagues, comparing their Myxococcus xan-
thus protein’s sequence to that of T. maritima’s encapsulin, found
the two were homologous.^13 And like the T. maritima particles,
the Myxo protein shells housed proteins that store iron. Two of the
proteins inside the compartments acted much like another iron
storage protein, ferritin, but the size of the nanocompartments
meant they could hold about 30,000 atoms of iron—10 times as
much as a ferritin complex.
Why would the bacterium need such iron stores? The
researchers found a clue when they took away nutrients. “When
we starved the cells, there were [many] more of the particles,”
recalls Hoiczyk. Hungry M. xanthus cells change their activ-
ity, coming together to form a fruiting body. The nanocompart-
ments, Hoiczyk says, “obviously play a role under that stress-
ful transition.” Specifically, the nanocompartments appear to
protect the cells from oxidative stress, as in T. maritima, addsMcHugh, who now has her own lab at the University of Califor-
nia, San Diego.
It turns out that, like microcompartments, encapsulin
nanocompartments may be relatively common. Last year,
Tobias Giessen, a postdoc in Pamela Silver’s laboratory at Har-
vard Medical School and the Wyss Institute for Biologically
Inspired Engineering, reported he’d identified more than 900
potential encapsulin systems in banked bacterial genomes. The
encapsulin shell and interior enzyme genes colocalized, or even
fused together, across 15 bacterial and 2 archaeal phyla.^14 In
the past year, his analysis has raised those numbers to more
than 2,000 encapsulin systems in 18 bacterial and 3 archaeal
phyla, he says.
Based on published information about the enzymes’ likely
functions, Giessen divided the compartments into three main
categories. The most common type contain peroxidases, which
process hydrogen peroxide and other organic peroxides.
Another large group houses iron-storage proteins, as do the M.