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combining SYnthetic Biology and chemistry to create novel CO2-fixing enzymes, ORGanelles and ORGanisms

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Green machine: how synthetic biology could build a better leaf

A project to redesign photosynthesis from scratch hopes to fix carbon faster and more efficiently than nature, offering benefits to agriculture and the climate.

Health

The 1972 synthesis of vitamin B12 was a Herculean effort, requiring the work of more than 100 researchers over 12 years. The solution was entirely impractical – it required 72 chemical steps and had a yield of 0.01 % – but building such a complex molecule from scratch greatly advanced the field of organic synthesis. Tobias Erb, coordinator of the EU-funded SYBORG project, compares this undertaking to his own research, that of redesigning photosynthesis from first principles. “The idea is to use synthetic biology to rethink CO2 fixation,” explains the professor of Biochemistry and Synthetic Metabolism at the Max Planck Institute for Terrestrial Microbiology. “CO2 fixation is central to biology, it is the process by which all living matter is formed, and at the same time, it is of utmost important in terms of humans for creating a sustainable world.” In living organisms, almost all carbon fixation is performed by plants via photosynthesis. By redesigning the process from scratch, Erb and his colleagues hope they can build a faster, more efficient version than the six naturally existing pathways that have evolved over the past few billion years.

Dark reaction

Erb’s approach is to draw the metabolic network based on pure chemistry, removing every biological condition. This holds an advantage over evolution, which must balance the optimisation of photosynthesis with other factors such as overcoming limited resources, and resistance to drought and disease. Erb’s team also had the advantage of being able to bring together enzymes – chiefly from bacteria – that were statistically unlikely to coincide naturally. “Nature optimises the one thing it found, and does not explore new solutions,” he adds. One such solution is the CETCH cycle, developed by Erb and his team during the SYBORG project. It is a synthetic alternative to the ‘dark reaction’, the stage of photosynthesis which doesn’t require light. Building it required identifying and sourcing 17 different enzymes that could work together. Notably, this new cycle dispenses with RuBisCO, an enzyme that is fundamental to photosynthesis but notoriously slow and haphazard. It was replaced by enoyl-CoA carboxylase/reductases (ECRs) that are 10 to 20 times faster.

Plug and play

Erb and his team are now working on embedding their CETCH cycle into a living cell, a process he likens to “running new software on existing hardware.” A less complicated alternative is to place it in synthetic chloroplasts. “I have no clue which of these two is better, I see pros and cons for both,” explains Erb. Synthetic biology is often compared to an engineering approach, using living systems as mechanical parts, but Erb says it is not so simple. “In biology, parts are not perfect, they make mistakes, there are side effects, biology is about building in redundancies,” he notes. “It’s all about learning how to design, build and operate a robust, new-to-nature system.” The project was supported by the European Research Council. It was complemented by the FutureAgriculture and GAIN4CROPS projects, which sought to apply the research to farming. “The strength of the ERC is it stimulates you to think progressively, to take risks, and investigate exciting new topics, new endeavours, that move science forward,” says Erb. “We have seen it is possible to build new-to-nature systems in 3 to 4 years that can compete with systems that have evolved over billions of years.”

Keywords

SYBORG, photosynthesis, synthetic, CETCH, cycle, enzyme, pathway, metabolic, carbon fixation, chloroplast

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