Researchers from Stanford University and Northwestern University have developed a groundbreaking artificial metabolism called the Reductive Formate Pathway (ReForm) that transforms waste carbon dioxide (CO2) into valuable biological building blocks. This innovative system, which operates entirely outside of living cells, can convert formate – a simple liquid molecule easily derived from atmospheric CO2 – into acetyl-CoA, a universal metabolite crucial for all living cells. As a proof of concept, the system was then used to convert acetyl-CoA into malate, a commercially significant chemical utilized in food, cosmetics, and biodegradable plastics.
Unlike natural metabolic processes, ReForm is entirely synthetic, built from engineered enzymes that perform reactions not naturally found. This cell-free approach allowed the team to rapidly screen 66 enzymes and over 3,000 enzyme variants, a process far more efficient than using live cells. The final pathway involves six reaction steps, each executed by a specific engineered enzyme, successfully converting formate into acetyl-CoA. The ability to precisely control enzyme concentrations and other conditions in this cell-free environment was key to its success.
This breakthrough is a significant advancement for synthetic biology and carbon recycling, paving the way for the development of sustainable, carbon-neutral fuels and materials. The team also demonstrated ReForm's capability to process other carbon-based inputs, including formaldehyde and methanol. The scientists emphasized the urgent need for cost-effective and environmentally sustainable methods to manage atmospheric CO2, viewing ReForm as a crucial step towards a carbon- and energy-efficient future. The study, co-led by Professor Michael Jewett and Assistant Professor Karim, was published in the journal Nature Chemical Engineering.
