38 THE SCIENTIST | the-scientist.com
COLLEEN MCHUGHnized,” says Cheryl Kerfeld, a structural biologist who splits her
time between one lab at Michigan State University and another
at the Lawrence Berkeley National Laboratory.
Preliminary studies suggest that nanocompartments assist
with stress responses, while microcompartments often have roles
in metabolism. And although the details remain murky, it’s becom-
ing clear that these structures create a specialized microenviron-
ment for a specific purpose, says Kerfeld: “I would define them as
organelles.” A growing number of researchers are now working to
understand what these organelles do. Kerfeld predicts that eventu-
ally, the population of people studying bacterial compartments “is
going to be as big as any eukaryotic organelle community.”The oddity of bacterial microcompartments
It was the geometry of microcompartments that first caught Ker-
feld’s eye. Attending cyanobacteria meetings in the early 2000s,
she noticed that researchers would exhibit micrographs of bac-
teria containing “crazy-looking bodies.” The three-dimensional
symmetry of the so-called “polyhedral bodies” was irresistible to
the structural biologist, who set out to crystallize the proteins that
made up their exterior.
Kerfeld, then a research scientist at the University of Califor-
nia, Los Angeles (UCLA), focused on carboxysomes, microcompart-
ments first observed in the 1950s.^2 They were known to perform car-
bon fixation, and under the microscope, they looked like viral shells,
or capsids, protein-based structures that encapsulate RNA or DNA.
But it wasn’t clear, at that time, whether carboxysomes were true
shells with an inner space for reaction components, or just geometri-
cal clumps of relevant enzymes and reactants, says UCLA structural
biologist Todd Yeates, Kerfeld’s former PhD advisor.Members of the Yeates lab debated whether the carboxysome
protein structure, given its similarity to that of viruses, would
resemble the folds in viral capsids. While Kerfeld did find that the
carboxysome proteins of the cyanobacteria Synechocystis formed
shell-like proteins, those who had argued against any similarity to
viruses were right: the amino acid–scale architecture of the car-
boxysomes differed from that of viral capsids. Individual proteins
formed hexagonal tiles that composed the 12 faces of the bacterial
structures. Many of these tiles contained pores, presumably to let
reactants in and products out.^3 “It was clear they were going to be
really sophisticated machines,” says Yeates.At the time, carboxysomes and another type of microcom-
partment called metabolosomes, discovered in the ’90s, were
thought to be rare oddities, says Kerfeld. To see if they could
find more, she and Yeates each went hunting through micro-
bial genomes for sequences encoding the proteins that make up
microcompartment shells.
Conveniently, researchers already knew that the genes for
the shell proteins tend to colocalize with the DNA that codes for
the enzymes the compartments will house.^4 Yeates’s group took
advantage of this fact to identify putative microcompartment
groupings of shell and inner enzyme genes and extrapolate their
potential functions. In 2013, the team delineated seven catego-
ries of microcompartments, including known carboxysomes and
metabolosomes as well as novel types, such as one apparently
involved in the metabolism of amino alcohols.^5 Separately, Ker-
feld, by now at Michigan State and Berkeley Lab, and her team
used a similar approach to identify 23 different types of micro-
compartments spread across 23 bacterial phyla, as they reported
the following year.^6
Now, Kerfeld and Markus Sutter in her Berkeley lab are
repeating the bioinformatic analysis and incorporating more
genomes, including those from uncultivated species. They’ve
already found more microcompartments, Kerfeld says. “The pro-
portion of bacteria that seem to make these is rising.” A couple
of species possess genes for six different kinds of microcompart-
ments, potentially giving them access to a complex metabolism.It’s becoming accepted, a lot, in the
last 10 or 20 years that the prokaryotic
cytoplasm is highly organized.
—Cheryl Kerfeld, Michigan State University
and Lawrence Berkeley National LaboratorySWISS CHEESE: In 2009, microbiologist Egbert Hoiczyk, then at Johns
Hopkins University, observed strange holes in cultures of Myxococcus
xanthus. He and his colleagues thought the spaces were caused by viruses
killing the bacteria, but closer investigation revealed something quite
different: 32-nanometer-wide structures known as nanocompartments.