A compact, genetically encoded photoenzyme, miniSOG, enables spatiotemporally controlled bioorthogonal deboronative hydroxylation of diverse organoboronates in live cells by producing localized super....

Akiyama, T. & Ojima, I. Catalytic Asymmetric Synthesis (John Wiley, 2022). Brimioulle, R., Lenhart, D., Maturi, M. M. & Bach, T. Enantioselective catalysis of photochemical reactions. Angew. Chem. Int. Ed. 54, 3872–3890 (2015). Silvi, M. & Melchiorre, P. Enhancing the...

Nature Catalysis, Published online: 24 October 2025; doi:10.1038/s41929-025-01433-3Artificial photobiocatalytic reactions are appealing but sometimes suffer from non-enzymatic side reactions. Now a photoenzyme for enantioselective [2 + 2] photocycloaddition of 2-naphthyl derivatives is reported and combined with designed quenchers that shut down the competing enzyme-free racemic reaction.

Nature Catalysis, Published online: 12 August 2025; doi:10.1038/s41929-025-01390-xExpanding the methods for constructing artificial enzymes is of high interest. Now a photoactive cofactor is designed that mimics NAD+, allowing its insertion into a range of NAD+-binding protein scaffolds to catalyse inter- and intramolecular [2 + 2] cycloaddition reactions.

Substrates and products were chemically synthesized according to procedures reported in the ‘Chemical procedures’ section of the Supplementary Information. All other chemicals and biological materials were obtained from commercial suppliers. Lysozyme, DNase I, chloramphenicol and kanamycin were purchased from Sigma-Aldrich...

Three PhD postiions in computational protein design

Three PhD postiions in computational protein design

C–N bond formation is integral to modern chemical synthesis due to the ubiquity of nitrogen heterocycles in small-molecule pharmaceuticals and agrochemicals. Alkene hydroamination with unactivated alkenes is an atom economical strategy for constructing these bonds. However, these reactions are challenging to render asymmetric when preparing fully substituted carbon stereocenters. Here, we report a photoenzymatic alkene hydroamination to prepare 2,2-disubstituted pyrrolidines by a Baeyer-Villiger Monooxygenase. Five rounds of protein engineering afforded a mutant, providing excellent product yield and stereoselectivity. Unlike related photochemical hydroaminations, which rely on the oxidation of the amine or alkene for C–N bond formation, this work exploits a through-space interaction of a reductively generated benzylic radical and the nitrogen lone pair. This antibonding interaction lowers the oxidation potential of the radical, enabling electron transfer to the flavin cofactor. Experiments indicate that the enzyme microenvironment is essential in enabling a novel C–N bond formation mechanism with no parallel in small molecule catalysis. Molecular dynamics simulations were performed to investigate the substrate in the enzyme active site which further support this hypothesis. This work is a rare example of an emerging mechanism in non-natural biocatalysis, where an enzyme has access to a mechanism that its individual components do not. Our study showcases the potential of enhancing emergent mechanisms using protein engineering to provide unique mechanistic solutions to unanswered challenges in chemical synthesis.