Nature study finds AI-redesigned proteins evolve into better enzymes than natural starting points
lucapinello · x · 2026-07-23
AI-redesigned protein starting points improve enzyme evolution
A Nature paper reports a workflow that combines ProteinMPNN sequence design with autonomous laboratory evolution to engineer enzymes with better properties than those evolved from natural proteins.
- The team redesigned three distinct botulinum neurotoxin proteases using AI-guided protein sequence design.
- Those redesigned variants showed improved stability and full catalytic efficiency.
- In side-by-side continuous evolution campaigns, the redesigned proteins consistently produced variants with higher activity than wild-type starting points.
- Across four evolution campaigns, the redesign opened access to otherwise unreachable functional sequences and sped up adaptation.
- In a final demonstration, the AI-redesigned protease achieved higher catalytic efficiency and stability while reducing native substrate cleavage, including 79× greater selected specificity for ataxin-2 than the best WT-derived variant.
The study argues that AI-redesigned starting points can expand the reachable protein fitness landscape and improve downstream enzyme engineering results.
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