Engineered enzymes forge carbon-carbon and carbon-nitrogen bonds with high selectivity

Scientists at the Manchester Institute of Biotechnology have engineered a new family of enzymes capable of forming multiple chemical bonds, such as carbon-carbon (C-C) and carbon-nitrogen (C-N), with exceptional selectivity. This breakthrough, detailed in the journal Nature Catalysis, addresses the challenge of creating biological catalysts that can selectively construct complex molecular architectures.

The artificial enzymes, termed allylic transferases, were developed by incorporating a non-natural catalytic amino acid, enabling them to form reactive intermediates and selectively bond with various carbon- and nitrogen-containing molecules. Directed evolution techniques improved the enzymes' performance, with one variant (ASB1.3) achieving over 99% conversion and high stereochemical purity.

The enzymes demonstrated versatility, working with a wide range of substrates, including substituted furans, indoles, pyrroles, cyanoesters, diketones, ketoesters, anilines, and isatins, without generating significant side products. Structural analysis revealed that a para-nitrophenol group in the enzyme active site aids in orienting reactants, enhancing stereoselectivity.

While further development is needed, this research expands the scope of biocatalysis by providing new avenues for producing challenging molecular structures that are difficult to synthesize using traditional small-molecule catalysts.