Scalable and High-Efficiency Cell-Free SAF Bioproduction

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About This Project

Sustainable Aviation Fuel offers a viable path to decarbonize long-haul flights. Fischer-Tropsch and Ethanol-to-Jet, two proposed routes to make SAF, are energetically- and carbon-inefficient, respectively. Instead, we propose a SAF production pathway based on a cell-free biomanufacturing system. Our process utilizes only one enzyme with no cofactors, allowing rapid scale-up for economic, net-zero SAF production.

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What is the context of this research?

This project aims to decarbonize the hard-to-abate aviation sector by making Sustainable Aviation Fuel. Batteries and hydrogen fuel cells used for ground transport have 1/10th the energy density of jet fuel and have no clear path to feasibility for long-haul flights. In contrast, SAF is a drop-in replacement for conventional jet fuel and requires almost no infrastructure or engine modifications.
To do this in a truly sustainable fashion, one needs a highly energetically efficient process that is cheap, commodity-level scalable, and decoupled from agriculture.

What is the significance of this project?

Aviation is responsible for 3% of global carbon emissions. The US and all major airlines have announced commitments to >50% SAF by 2050, but no clear path exists for SAF production at scale. This proposal involves merging advanced TRL-9 methods with a high-risk, high-reward biological step to get there fast and efficiently. We opt for a cell-free system driven by a single enzyme, devoid of cofactors, to enhance scalability. Our focus on catalyzing SAF-compatible carbon chains ensures scalability becomes a matter of "when" rather than "how." Similar processes achieved at a commodity scale, like lactase for lactose-free milk or high fructose corn syrup production, emphasize the potential reach of our enzyme, extending well beyond sustainable aviation fuel.

What are the goals of the project?

Our aim is to showcase a novel enzymatic process, enabling the creation of SAF-compatible long carbon chains. Specifically, we seek to catalyze a carbon-carbon bond formation between precursor molecules, sourced directly from CO2 and hydrogen. The initial step involves enzymatically condensing two precursor molecules, a formidable challenge as nature relies on costly cofactors to do this naturally. Our objective is to design an enzyme that is free from co-factors, employing synthetic biology tools for further optimization and advancing toward long carbon chain polymerization.


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At the heart of our proposal is a single enzyme that polymerizes precursor molecules into long carbon chains, bypassing the need for expensive cofactors. Our goal for this grant is to demonstrate a single condensation reaction between two precursor molecules. Follow-up work will be required to establish polymerization, but we note that according to our analysis, no physicochemical constraint exists. We will achieve our goal by computationally designing a protein library, testing around 100 candidates, and thoroughly characterizing enzymes displaying the desired activity. While our approach is novel, we anticipate potential matches in near-naturally occurring enzymes. Rational protein engineering and mid-throughput screening will guide us in identifying promising candidates for further refinement. This process holds promise for sustainable aviation and beyond.

Project Timeline

This 3-4 month project aims at discovering enzymes with our desired activity. this grant aims to derisk our key hypothesis - that such enzymatic activity is possible. If it is, it opens many possibilities, but most excitingly for us, it paves a path for further optimization to establish affordable and scalable SAF production.

Nov 15, 2023

Map natural diversity.

Nov 30, 2023

Design library and order genes.

Dec 31, 2023

Express and purify ±100 enzymes.

Jan 31, 2024

Establish enzymatic assay and test activity.

Feb 29, 2024

Biochemical characerization of leading candidates

Meet the Team

Dan Davidi
Dan Davidi

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Dan Davidi

Dan is a synthetic biology expert specializing in metabolic modeling, enzyme evolution, and systems biology. He holds a Ph.D. in systems biology from the Weizmann Institute of Science, working with Prof. Ron Milo to develop new metabolic modeling tools and applying them to improve biological carbon fixation. After a postdoc at the genetics department of Harvard Medical School, he established a new center for Synthetic biology at Harvard (the Hive) and served as its associate director. Working closely with Prof. Pamela Silver, Dan developed, among other technologies, synthetic and bionic photosynthetic systems by coupling microbial growth to photovoltaic energy sources. During his time at Amazon's moonshot factory, he served as the design and computational synthetic-biology lead, working toward optimizing microbial bioproduction at scale from CO2-derived feedstocks, and specifically focusing on SAF. Dan worked with top researchers in the field, government officials, and leading synthetic biology companies throughout his career. He published 22 peer-reviewed papers in high-impact journals that were cited >2700 times. He is currently an Entraprenuer in Residance at, - a leading venture capital firm in Israel. Dan wears other 'ecosystem hats and is very involved in nation-level, strategic initiatives to build deep technological innovation in Israel.

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