Enantiodivergent Evolution of a De Novo Protein for Enzymatic [2 + 2] Photocycloaddition Activity The design of artificial photoenzymes by incorporating synthetic chromophores into proteins represents a promising strategy to achieve non-natural biocatalytic transformations with high levels of ster...

Excited to share our newest ACS Catalysis paper @pubs.acs.org from Benny, jointly from our lab and @cathleenzeymer.bsky.social on the enantiodivergent evolution of a de novo protein for [2+2] photocycloadditions! 💡🙌
#photochemistry #photoenzyme #biocatalysis 💡🙌

Efficient and selective energy transfer photoenzymes powered by visible light - Nature Chemistry Recent studies have shown that energy transfer photoenzymes can be engineered to promote stereocontrolled [2 + 2] cycloadditions; however, existing systems rely on ultraviolet light and display limite...

Amazing work, Johannes! Check out his contribution to the work of the Green Group from @uommib.bsky.social on ennatioselective photoenzymatic C-H insertion of quinolones, out now in @natchem.nature.com! #photochemistry #photoenzyme #enantioselective💡🧬🥳

www.nature.com/articles/s41...

Protein-Driven Electron-Transfer Process in a Fatty Acid Photodecarboxylase Naturally occurring photoenzymes are rare in nature, but among them, fatty acid photodecarboxylases derived from Chlorella variabilis (CvFAPs) have emerged as promising photobiocatalysts capable of performing the redox-neutral, light-induced decarboxylation of free fatty acids (FAs) into C1-shortened n-alka(e)nes. Using a hybrid QM/MM approach combined with a polarizable embedding scheme, we identify the structural changes of the active site and determine the energetic landscape of the forward electron transfer (fET) from the FA substrate to the excited flavin adenine dinucleotide. We obtain a charge-transfer diradical structure where a water molecule rearranges spontaneously to form a H-bond interaction with the excited flavin, while the FA’s carboxylate group twists and migrates away from it. Together, these structural modifications provide the driving force necessary for the fET to proceed in a downhill direction. Moreover, by examining the R451K mutant where the FA substrate is farther from the flavin core, we show that the marked reduction of the electronic coupling is counterbalanced by an increased driving force, resulting in a fET lifetime similar to the WT, thereby suggesting a resilience of the process to this mutation. Finally, through QM/MM molecular dynamic simulations, we reveal that, following fET, the decarboxylation of the FA radical occurs within tens of picoseconds, overcoming an energy barrier of ∼0.1 eV. Overall, by providing an atomistic characterization of the photoactivation of CvFAP, this work can be used for future protein engineering.

Our computational study on a fatty acid photodecarboxylase is out in JACS Au #openaccess.

Check out what drives the electron transfer and decarboxylation in this exciting #photoenzyme!

pubs.acs.org/doi/10.1021/...

#QMMM #compchem #photobiocatalysis

Congrats to Giacomo and all authors!