TOBIAS J ERB
Global
carbon cycling
Despite its recognition as a major greenhouse gas, atmospheric
carbon dioxide also provides a convenient and valuable source
of carbon. In this engaging interview, Tobias J Erb discusses
his efforts to mine that source, the potential for synthetic
biological applications and funding challenges in Switzerland
However, fossil fuels, which we are currently
exploiting at high intensity, are also the result
of carbon fixation processes over millions and
billions of years.
While high concentrations of atmospheric
CO2 are generally seen as negative, your
work highlights the potential of utilising
this readily available carbon source.
What previous efforts have been made in
this field?
Your research examines the interface
between microbial physiology and
biochemistry. What is your professional
background, and what led to your work in
this area?
I am a trained chemist and biologist, so it
feels natural for me to do research at the
interface of both. I have always been fascinated
by nature’s mechanisms of catalysing
challenging chemical reactions. In this context,
microorganisms are true ‘world champions’.
While invisible to the human eye, they shape
all life on Earth. They convert gigatonnes
(Gt) of nitrogen, atmospheric carbon dioxide
(CO2) and methane, which makes them key
players in the global cycling of elements. My
passion for microbial biochemistry was evoked
by my desire to understand the chemical
fundamentals of the biological processes that
enable life.
Research on carbon fixation is quite active,
as CO2 is a potent greenhouse gas. From a
chemical point of view, CO2 is highly oxidised
and relatively inert, so a large energy input or
harsh conditions are required for its fixation
in the absence of efficient catalysts. Current
chemistry, however, lacks such catalysts. As a
consequence, only 0.1 Gt of CO2 per year are
converted into value-added products through
the chemical industry.
In contrast, the biological transformation
of CO2 is carried out under mild conditions
and accounts for approximately 100 Gt/year.
Several novel microbial pathways and enzymes
for CO2 fixation have been identified in recent
years. The practical application of these
enzymes, however, remains limited because
many carboxylases are highly substrate specific
and often require complex cofactors.
What are the major aims of your project and
how do you hope to achieve these?
Can you explain the term ‘carbon fixation’?
Our research on CO2 fixation has two
directions. Firstly, we will study the details of
enzymatic CO2 fixation to learn from these
highly efficient biocatalysts. We will then
apply this knowledge to engineer novel CO2
fixation reactions.
Carbon fixation is the conversion of inorganic
carbon into organic molecules. It is the key
process in the global carbon cycle that allows
for biomass production from CO2 and sustains
life. The most evident carbon fixation process
affecting human life is the cultivation of
plants for food and bioethanol production.
Secondly, we are interested in discovering and
analysing novel pathways for CO2 fixation
in the global carbon cycle. Studying the
fundamental principles that form and shape
these natural pathways, our latest efforts
make use of synthetic biology methods to
combine different enzymes and reactions in
selected model systems so that we can design,
construct and explore CO2 fixation pathways
that have not yet been invented by nature.
Does this work have applications in
biotechnological and medical disciplines?
Max Planck once stated: “Knowledge must
precede application”. Our research follows
this principle and aims to answer fundamental
biological questions, but we are also interested
in translating our discoveries into application.
For example, we recently realised that
reductive carboxylases are important building
blocks in the biosynthesis of numerous
antibiotics, immunosuppressants and other
bioactive compounds. This may open the
door to the targeted modification of these
compounds, enabling the production of
designer drugs in the future. Similarly,
synthetic CO2 fixation pathways in
production strains could pave the way to the
biotechnological production of value-added
products from CO2.
Following the recent referendum on
immigration, Switzerland has been
reclassified as an ‘industrialised third
country’ when it comes to securing EU
funding. How will this affect your work and
that of your colleagues?
The vote has already had direct impact
on my research, as I was preparing a grant
application at the time and was suddenly no
longer eligible for EU funding. Although the
Swiss Government reacted quickly to install
an alternative funding scheme, this can only
be a temporary solution for both Switzerland
and the EU. Due to the country’s strong ties
to the European research community, Swiss
researchers need reliable integration into
the EU research network, and the EU needs
Switzerland as a research-intensive partner of
high innovative potential. Moreover, being born
and raised in the border triangle of Germany,
Switzerland and France, I am also personally
convinced that big scientific challenges can
only be solved with European efforts.
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TOBIAS J ERB
Inspired by nature
Researchers from the Swiss Federal Institute of Technology (ETH Zürich) are studying the principles of biological
carbon dioxide fixation. Their work aims to discover and redesign novel carbon fixing enzymes and pathways
CARBON DIOXIDE (CO2) is arguably the most
important greenhouse gas. It is responsible for
60 per cent of the ‘enhanced greenhouse effect’,
which underlies global warming, and has steadily
been increasing in recent years. However,
atmospheric CO2 is also an inexpensive and
readily-available carbon source that can be used
to synthesise products of benefit to society.
Because chemical carbon fixation reactions
generally require very harsh conditions, few
synthetic processes have been developed that
utilise CO2. By contrast, biology offers remarkably
efficient methods of doing so. Microorganisms
have carboxylating (carbon fixing) enzymes able
to convert CO2 into organic compounds under
mild conditions, and have the potential to be
exploited in biotechnological processes.
Despite their fundamental role in the global
carbon cycle, less than 1 per cent of all
microorganisms have been studied in detail
and many enzymes remain undiscovered.
Dr Tobias J Erb, Junior Group Leader in the
Institute of Microbiology at the Swiss Federal
Institute of Technology (ETH Zürich), aims to
change this. He is fascinated by the creativity
and complexity of nature, and has dedicated
his career to searching for novel biochemical
reactions and pathways.
OVERLOOKED PRINCIPLES
Before joining ETH Zürich in 2011, Erb had
already built a strong research foundation and
made important contributions to his field: “In
the laboratories of Professors Birgit Alber and
Georg Fuchs, I discovered a class of reductive
carboxylases in bacteria that represent a
completely novel principle of CO2 fixation. We
now know that these enzymes are among the
most efficient CO2 fixing enzymes,” he explains.
“These microbial carboxylases are 10 times faster
than the CO2 fixing enzymes used by plants.”
14INTERNATIONAL INNOVATION
cofactors function remain hazy. Now, Erb’s work
has shed important new light on the function of
one of nature’s most common cofactors.
While obviously benefiting metabolism, the
speed of catalysis makes it challenging to
study individual enzyme processess. In order to
make this possible for CCR, the team slowed
the enzyme’s reactivity by cooling it. Then,
by partnering with the Organic Chemistry
Department at ETH Zürich, they were able to
follow the decelerated reaction in real time using
nuclear magnetic resonance (NMR).
Active site of a reductive carboxylase with its substrates
before the addition of CO2.
Currently, Erb and his team are investigating
the molecular mechanisms that enable
reductive carboxylases to bind CO2 and promote
carboxylation. He hopes to learn from the
CO2 fixation biochemistry of these enzymes
to engineer carboxylation function in other
protein scaffolds, creating novel catalysts for
biotechnological or industrial use. In order to
better understand the high level of efficiency
of reductive carboxylases, Erb’s team recently
developed tools that enable them to dissect the
individual steps of enzyme reactions, allowing
them to follow CO2 fixation in slow motion.
STEP BY STEP
Indeed, late last year the group was able to
analyse the interplay between enzymes and
their cofactors in unprecedented resolution. The
researchers studied the reaction of crotonylCoA carboxylase/reductase (CCR), one of the
fastest CO2 fixing enzymes on Earth. Similar
to 15 per cent of all enzymes, CCR requires a
nicotinamide cofactor. Although discovered over
100 years ago, the details of how nicotinamide
The results, published in Nature Chemical
Biology, provided experimental evidence
for a 50-year-old hypothesis: nicotinamidedependent enzyme reactions take place in
defined steps. Moreover, the team was not only
able to detect the intermediate products but
could also isolate them, opening new avenues of
enzyme research. These products could be used
as molecular probes, and modifying them could
lead to novel enzyme inhibitors, potentially
generating new therapeutics.
PROTEIN EVOLUTION
Another focus of Erb’s research is the nature of
carboxylase evolution: “Because all life depends
on biomass formation, the capability to fix CO2
must have been one of the earliest inventions,”
he reveals. “However, since then, life has
occupied many different ecological niches. This
likely caused the evolution of novel CO2 fixing
proteins and pathways specifically adopted to
the new conditions.” In order to understand this
process, Erb studied ribulose-1,5-bisphosphate
carboxylase/oxygenase (rubisco) – likely the
most abundant protein on Earth today. It
accounts for over 20 per cent of the total amount
of protein in plant leaves, where it catalyses the
first major step of carbon fixation.
Rubisco is present in bacteria, eukaryotes
and even archaea, and therefore must
have emerged early in evolution when the
atmosphere was rich in CO2 and almost devoid
of oxygen. Building on this, Erb’s research
showed that today’s rubisco is closely related to
simple isomerases – enzymes that catalyse the
structural rearrangement of molecules. Rubisco
was therefore not originally a CO2 fixing
enzyme, and Erb argues that this is the case for
other enzymes as well: “More recently, we have
found evidence that reductive carboxylases,
such as CCR, evolved from ordinary reductases
into CO2 fixing enzymes. This demonstrates the
incredible potential of nature to evolve catalytic
activities for novel biological functionalities”.
TRULY NOVEL BIOLOGY
At present, Erb’s group is combining their
biochemical and evolutionary understanding of
carbon fixing enzymes to redesign entirely new
ones. In a pilot project funded by the Gebert Rüf
Foundation, the researchers are breaking new
ground by exploring the possibility of creating
designer carboxylases that might open up new
biotechnological and applied perspectives, for
example, by providing novel building blocks for
antibiotic synthesis.
Erb and his team are also currently developing
platforms to create artificial CO2 fixation
cycles. They aim to design highly efficient CO2
fixation routes de novo with synthetic biology
by combining suitable
enzymes from the more
than
5,000
different
metabolic reactions that
have previously been
discovered. These synthetic
CO2 fixation pathways could
serve as first steps for the development
of CO2 fixing modules and set the stage for
the bottom-up design of self-sustaining
synthetic microbial cells.
Although there are roadblocks ahead, Erb’s
work could initiate a paradigm shift in biology:
“Creating novel biology is a major challenge;
this is not only true for our efforts but for
biology in general. For a long time, biology has
been mainly descriptive but the next big leap is
to convert it into a truly applicable discipline.
Only if we are able to construct novel
biology have we understood its fundamental
principles,” he concludes.
Erb is working to design entirely
new carboxylases, which could
provide novel building blocks for
antibiotic synthesis
INTELLIGENCE
MICROBIAL CO2 FIXATION: FROM
UNDERSTANDING TO APPLICATION
OBJECTIVES
• To discover new principles and mechanisms
at the interface of microbial physiology
and biochemistry
• To identify novel processes in the global
carbon cycle
• To identify the molecular and
evolutionary mechanisms that allow
proteins to bind CO2 and to promote
carboxylation reactions
• To mimic evolution by constructing and
exploring artificial CO2 fixation pathways
that have not yet been invented by nature
KEY COLLABORATORS
Julia Vorholt; Patrick Kiefer, Institute of
Microbiology, Swiss Federal Institute of
Technology (ETH Zürich), Switzerland •
Marc-Olivier Ebert; Detlef Günther; Bodo
Hattendorf, Department of Chemistry, ETH
Zürich • Ivan Berg; Georg Fuchs, Albert
Ludwigs University of Freiburg, Germany •
John Gerlt, University of Illinois at UrbanaChampaign, USA • Birgit Alber; Robert
Tabita, The Ohio State University, USA
FUNDING
Gebert Rüf Foundation • ETH Zürich • Swiss
National Science Foundation (SNSF) •
German Research Foundation (DFG) • Die
Junge Akademie
CONTACT
Dr Tobias J Erb
Junior Group Leader
Institute of Microbiology HCI F 437
Vladimir-Prelog-Weg 4
8093 Zurich
Switzerland
T +41 44 632 3654
E [email protected]
www.grstiftung.ch/de/portfolio/projekte/
alle/y_2012/GRS-062-12.html
http://p3.snf.ch/project-136828
Redeeming a biological principle
In 2010, a team of US biologists claimed to find a new microorganism, named GFAJ-1,
that was not only undamaged by arsenic, but could also use it in place of phosphorous
to create macromolecules such as DNA
This finding sent shockwaves through the scientific community. It challenged the dogma
that all life on Earth is made from six basic building blocks (carbon, hydrogen, oxygen,
nitrogen, sulphur and phosphorus) and led to speculations on how extraterrestrial life
might be sustained.
TOBIAS J ERB earned his PhD in 2009
working at the University of Freiburg,
Germany, and The Ohio State University,
USA. After postdoctoral training at the
Institute of Genomic Biology, University of
Illinois, USA, he joined ETH Zürich in 2011,
where he became Junior Group Leader at
the Institute of Microbiology funded by the
AMBIZIONE-Program of the SNSF. In 2013,
Erb was elected as a member of the Junge
Akademie and awarded the Swiss Society of
Microbiology Encouragement Award.
At the Swiss Federal Institute of Technology (ETH Zürich), Tobias Erb, Julia Vorholt and
Detlef Günther became interested in this unusual organism and set out to investigate its
biochemistry in detail. However, they were unable to detect any traces of arsenic in the
DNA of GFAJ-1 and showed that the bacterium had functioning phosphate metabolism.
Based on their results, the scientists concluded that the central dogma remains valid
for GFAJ-1, closing the debate as to whether life is possible beyond the six fundamental
elements. “Looking for new biological principles sometimes simply results in confirming
existing ones,” Erb reflects.
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