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Atom Transfer Radical Polymerization of Functionalized Vinyl Monomers Using Perylene as a Visible Light Photocatalyst
Published on: April 22, 2016
Repurposing Thiamine-Dependent Benzaldehyde Lyases as Visible-Light-Driven Radical Acyltransferases
Yuanyuan Xu1,2, Xichao Peng1, Xiaoqiang Huang1
1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Frontier Interdisciplinary Science Research Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing210023, China.
Accounts of Chemical Research
|July 13, 2026
Summary
Researchers developed a synergistic photoredox/thiamine radical biocatalysis to achieve asymmetric radical acylations. This novel approach repurposes thiamine diphosphate (ThDP)-dependent enzymes for challenging radical transformations with high stereochemical control.
Area of Science:
- Biocatalysis and Organic Synthesis
- Enzyme Engineering and Mechanistic Enzymology
Background:
- Thiamine diphosphate (ThDP)-dependent enzymes are crucial for C-C bond formation via umpolung mechanisms.
- Existing biomimetic N-heterocyclic carbene (NHC) catalysts struggle with enantioselective cross-coupling of prochiral radicals due to intermediate reactivity and chiral environment limitations.
- Previous ThDP enzyme pathways were primarily two-electron processes, with only a few known radical pathways (e.g., PFOR) not yet applied to asymmetric radical reactions.
Purpose of the Study:
- To develop a synergistic photoredox/thiamine radical biocatalysis for asymmetric radical acylations.
- To overcome the challenge of stereochemical control in enantioselective cross-coupling involving prochiral C-centered radicals.
- To repurpose ThDP-dependent enzymes, specifically benzaldehyde lyase (PfBAL), into versatile radical acyltransferases (RATs).
Main Methods:
- Integration of visible-light photoredox catalysis with a thiamine-dependent enzyme (Pseudomonas fluorescens PfBAL).
- Activation of aldehyde substrates by PfBAL to form enzymatic Breslow intermediates.
- Concurrent generation of prochiral C-centered radicals and enzyme-bound thiamine-derived ketyl radicals via photoredox catalysis.
- Protein engineering of PfBAL to create a precise chiral environment for enantioselective radical cross-coupling.
Main Results:
- Successful demonstration of synergistic photoredox/thiamine radical catalysis for decarboxylative radical acylation using N-(acyloxy)phthalimides and benzaldehyde.
- Extension of the methodology to diverse challenging transformations, including C(sp3)-H acylation, acylation via nitrogen-centered radicals, and three-component couplings.
- Construction of all-carbon quaternary stereocenters with minimally differentiated alkyl substituents.
- Identification of key residues (480 and 481) in PfBAL through protein engineering and computational studies responsible for high enantioselectivity.
Conclusions:
- Repurposed ThDP-dependent PfBAL into a versatile radical acyltransferase (RAT), expanding enzymatic reactivity.
- Established a generalizable platform for controlling fleeting radical intermediates using a combination of chemomimetic and biomimetic strategies.
- Demonstrated the potential for future advancements using AI-assisted protein design for broader applications of thiamine-dependent enzymes.
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