NLR Doubles Terpene Yields Using Cell-Free Enzymes
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- NLR researchers are pioneering cell-free biomanufacturing, dumping handpicked, cell-free-optimized enzymes — called 'exozymes' — into bioreactors with sugars from corn stover and wood chips to produce target chemicals without microbial cells, organelles, or DNA.
- Thermophilic enzymes sourced from extreme environments operated six times longer than bacterial enzymes and nearly doubled terpene yields in a collaboration with industrial partner eXoZymes Inc., with much higher solvent tolerance — yields Bomble called 'nearly unheard of' using a microbial chassis.
- High-throughput liquid-handling robots in NLR's Field Test Laboratory Building can prepare samples of over 1,000 enzyme variants in under an hour, enabling the team to capture several thousand data points per day and feed them into AI-driven screening for promising enzyme designs.
- NLR has been issued over 294 biotechnology patents since 2020, and the lab's cell-free biomanufacturing R&D program has been running for the past five years alongside the nearly $70 billion U.S. biofuels economy that produces around 17 billion gallons of ethanol annually via microbial methods.
- Cofactor costs are the second-biggest expense driver in productive cell-free systems for commodity chemicals, and NLR has expanded a synthetic nicotinamide cofactor library from 132 candidates in a 2025 Green Chemistry paper to more than 1,000, using density functional theory and AI to predict properties before synthesis.
- Principal scientist Yannick Bomble said the core challenge is engineering enzyme systems that sustain high yields on cue at a price point attractive to industry, requiring enzymes that remain stable for days, are tunable for precise reactions, and can be manufactured at scale.
- The cell-free approach eliminates background metabolic processes entirely, giving researchers control over every reaction step — and Bomble said it could transform not just the bioenergy sector but also pharma and fine chemicals.
Why it matters: If NLR can stabilize engineered enzyme cascades and drive cofactor costs down, cell-free biomanufacturing could unlock chemical production routes that living-cell systems can't efficiently run — including the near-doubling of terpene yields already demonstrated with thermophilic enzymes. That matters for the multi-billion-dollar biofuels industry and adjacent pharma and fine-chemicals markets that currently rely on microbial fermentation with built-in yield and toxicity constraints.
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