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 CO2 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 C1 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.

Mark Stitt (Director, MPI-MP) and Ron Milo (Weizmann Institute of Science)