Replacing chemical plants with methanol-eating bacteria

Contributors:

Dr. Ronja Rappold

Dr. Kevin Hares

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In this episode of Innovate and React, I welcome Dr. Ronja Rappold, co-founder of TENO Bioworks, to explore how microorganisms and synthetic biology can transform alternative carbon sources into high-value chemicals. While biological manufacturing is well known for producing life-saving pharmaceuticals like insulin or traditional fermented goods, shifting base and fine chemical production away from fossil fuels presents a unique challenge. Relying solely on agricultural sugars introduces significant “food vs. fuel” conflicts and risks breaching critical planetary boundaries, including land use, freshwater consumption, and nutrient cycles. Ronja and her team address this by targeting C1 feedstocks—specifically green methanol derived from captured CO₂.
How do you teach an industrial workhorse to live on a completely foreign feedstock? Ronja explains TENO Bioworks’ approach to performing a metabolic “heart transplant” on Escherichia coli (E. coli). They successfully rewired E. coli to utilize methanol as its primary carbon and energy source. We also dive into the downstream engineering required to produce target chemicals like lactic acid, the advantages of using raw, unpurified methanol over traditional metal catalysts.

• 01:07 – Introduction to Biotechnology: Ancient Fermentation & Modern Molecular Tools
• 05:19 – The Limits of Sugar Feedstocks & The Planetary Boundaries Framework
• 12:02 – Metabolic Rewiring: Teaching E. coli to Live on Methanol
• 16:36 – Adaptive Laboratory Evolution (ALE) in Bioreactor Systems
• 26:19 – Process Advantages of Utilizing Unpurified Raw Methanol

Here you can find the fluorescence microscopy image: https://innovateandreact.com/fluorescence-microscopy-image/

Here you can learn more about TENO and their research:

• P. Keller, E. Hegedis, B. Jäger, S. H. Rüdisser, H. Schultz, L. A. Büchel, A. M. Ochsner, T. Bradley, M. A. Reiter, D. Hilvert, J. A. Vorholt, “Identification of overoxidizing and non-overoxidizing NAD-dependent methanol dehydrogenases and implications for synthetic methylotrophy” Nat Commun 2025, 16, 10967. https://doi.org/10.1038/s41467-025-65949-9
• M. A. Reiter, T. Bradley, L. A. Büchel, P. Keller, E. Hegedis, T. Gassler, J. A. Vorholt, “A synthetic methylotrophic Escherichia coli as a chassis for bioproduction from methanol” Nat Catal 2024, 7, 560–573. https://doi.org/10.1038/s41929-024-01137-0
• P. Keller, M. A. Reiter, P. Kiefer, T. Gassler, L. Hemmerle, P. Christen, E. Noor, J. A. Vorholt, “Generation of an Escherichia coli strain growing on methanol via the ribulose monophosphate cycle” Nat Commun 2022, 13, 5243. https://doi.org/10.1038/s41467-022-32744-9
• About Teno: https://ethz.ch/en/news-and-events/eth-news/news/2026/06/bacterial-factories-a-key-to-climate-friendly-chemistry.html
• About the technology: https://ethz.ch/en/news-and-events/eth-news/news/2024/04/bacteria-for-climate-neutral-chemicals-of-the-future.html

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