Summary
Researchers used generative protein design and directed evolution to create artificial metalloenzymes that control the stereochemistry of light-driven reactions. The study reports diverse reactions, catalyst recycling and high turnover.
Researchers have designed protein scaffolds that bind synthetic metal photocatalysts, then used directed evolution to make the resulting hybrid catalysts highly selective for one molecular handedness. The Nature study reports that these artificial metalloenzymes support diverse light-driven reactions, high catalyst turnover and recycling, including with commercially available racemic metal complexes.
How the protein controls the reaction
An artificial metalloenzyme combines a synthetic metal cofactor with a protein scaffold. Here, the researchers used generative protein design to create scaffolds that bind metal polypyridine photocatalysts—light-absorbing complexes used to drive chemical reactions. They then applied directed evolution, iteratively changing and selecting protein variants, to improve the catalysts’ performance and selectivity.
The goal was enantioselectivity: favouring one of two mirror-image forms of a product. These forms can have different properties, so controlling which one a reaction produces is important in asymmetric synthesis. The protein provides a structured environment around the metal cofactor, rather than leaving the metal complex to operate in solution alone.
Spectroscopic studies, as reported by the authors, indicate that the protein environment lengthens the photocatalyst’s excited-state lifetime and positions a substrate near the cofactor. The authors link these effects to changes in energy transfer and to control over the reaction’s stereoselectivity.
Combining design with evolution
The work pairs computationally guided creation of new protein scaffolds with laboratory evolution. That combination addresses a challenge for artificial metalloenzymes: existing proteins may not naturally provide suitable binding sites for synthetic catalysts, while finding useful scaffolds by trial and error can be difficult.
The reported use of racemic metal complexes is notable because the protein environment can provide selectivity even when the starting metal catalyst is a mixture of forms. The authors present the approach as a way to build protein partners for synthetic metal complexes that lack natural protein counterparts, extending protein-based catalysis to reactions not served by existing enzymes.
The article was published online on 21 October 2026 as an early version of accepted research; Nature says it is citable and will be replaced by the final Version of Record. The abstract reports high turnover and recycling but gives no numerical values or reaction-specific selectivity data, limiting quantitative comparison.