Obituary for Arren Bar-Even

September 29, 2020

With great sadness, we have to announce the sudden, untimely and tragic death of our colleague Arren Bar-Even who passed away last week at the age of 40.

An Appreciation of Arren Bar-Even

With great sadness, we have to announce the sudden, untimely and tragic death of our colleague
Arren Bar-Even.
Arren was a totally dedicated, highly creative and vibrant scientist. In Arren’s own words, his research
‘focused on the design and implementation of novel metabolic pathways with the potential to directly
tackle humanity’s grand challenges of establishing a circular carbon economy and achieving
agricultural sustainability’. He was a rising star and his death is a great loss for the scientific
community. Beyond that, he was also a very special person of charisma, who created excitement and
vitality around him.
Arren was born in Haifa, Israel, and completed a Bachelor at the Technion (the Israeli Institute of
Technology) in 2002 and an MSc with Yitzhak Pilpel and Naama Barkai at the Weizmann Institute in
2005. After 4 years heading the R&D department of the biotech startup company SegaChem, he joined
the group of Ron Milo at the Weizmann Institute and worked for his PhD between 2009-2012, followed
by a short Postdoc. In March 2015 he was appointed leader of an Independent Max Planck Research
Group at the Max Planck Institute of Molecular Plant Physiology in Potsdam-Golm.
Already in his PhD, Arren made groundbreaking advances in metabolic engineering. He made a signal
contribution to our basic understanding of the general features of enzymes and metabolic pathways,
in a series of insightful meta-analyses of key design principles of metabolism. These included
integrative analyses of how evolutionary and physico-chemical trends shape enzyme kinetics, how
thermodynamic constraints shape the evolution of metabolic pathways, and how the hydrophobicity
and charge shape cellular metabolite concentrations. This deep grasp of the fundamentals of how
metabolism operates and evolves was a basis for his extraordinary advances in metabolic engineering.
These started in his time at the Weizmann, where he revealed to the world a myriad of novel pathways
that could lead to efficient carbon fixation, all based on his intimate and wide knowledge of existing
natural enzymes, but creatively rewired in synthetic pathways that he designed and analyzed. By that
Arren opened the path to synthetic biology of carbon fixation. He also came up with the key ideas
needed for the establishment of the Calvin-Benson cycle – the route by which CO
2 is assimilated in
algae and plants – in
E. coli.
During his all too brief time in Golm, his research followed several goals, all approaching his dream of
contributing to establishing a circular carbon economy.
The first was to engineer biotechnological organisms to enable growth on C
1 compounds like formate
or methanol as sole carbon source. Formate can be efficiently produced via electrochemical reduction
of CO2
, photoreduction of CO2, and hydrogenation of CO2. Methanol can be efficiently produced in a
two-step process, where electrochemically produced hydrogen reacts with CO2
. A model organism
growing on formate or methanol would pave the way to bio-refineries that are unlimited by feedstock
availability. He established novel pathways for formate assimilation in E. coli and other microbes, and
was on the way to optimizing these pathways and creating strains with efficient growth and the ability
to produce a range of valuable chemicals from them. The latter – implementing novel pathways to
produce valuable chemicals and energy sources, formed a second thread of his research.

Another goal was to design, analyze and implement novel pathways to boost plant carbon fixation and
crop productivity. One focus here was to decrease energy wastage during photosynthesis due to a
linked process termed photorespiration. The key enzyme that fixes CO2
in the Calvin-Benson cycle,
Rubisco, has a side reaction with oxygen, leading to formation of glycolate. This glycolate must be
recycled, and the endogenous pathway is wasteful as it leads to release of CO2
. Many groups
worldwide are trying to modify this pathway to make it less wasteful. Arren took a much more radical
approach, and designed several completely novel (or synthetic) pathways that could recycle glycolate
without this leading to carbon release. He explored these pathways in bacteria, and was starting to
implement the most promising one in photosynthetic organisms. In an even more ambitious project,
Arren set out to replace the Calvin-Benson cycle with a novel synthetic carbon-fixing pathway, which
theoretical analyses suggested would be more efficient that the Calvin-Benson cycle. He was on the
brink of establishing novel pathways in plants to improve photosynthesis when he died
In parallel with the pursuit of these specific engineering projects, he aimed to uncover the design
principles of cellular metabolism, which was also the title of his thesis dissertation. He was convinced
that replacing central metabolism pathways with synthetic alternatives would serve as a powerful tool
to explore and test the biochemical logic of metabolism and that this, in turn, would help us to better
understand the limitations and possibilities of metabolic engineering.
Arren was not only a brilliant scientist, he was also a very special person. This is captured in the
following contributions from his group members and colleagues.

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