Recently, the research team of Fengzhong Wang, the innovation team of food nutrition and functional factor utilization, gave insight into this research field by classifying the existing photocatalyst-enzyme hybrid systems into three section based on different hybridizing modes between photo-and enzymatic catalysis, and unlocks non-native new catalytic function of enzymes and expand the repertoire of enzymatic reaction. The relevant research results were published in the journal Biotechnology Advances (IF: 14.227) with the title “Photocatalyst-enzyme hybrid systems for light-driven bio transformation”.

Enzymes catalyse target reactions under mild conditions with high efficiency, as well as excellent regional-, stereo-, and enantiomeric selectivity. Photocatalysis utilises sustainable and environment-friendly light power to realise efficient chemical conversion. By combining the interdisciplinary advantages of photo- and enzymatic catalysis, the photocatalyst-enzyme hybrid systems have proceeded various light-driven biotransformation with high efficiency under environmentally benign conditions. According to their understanding of electron transfer from photocatalyst to enzyme, the construction schemes of the photocatalyst-enzyme hybrid systems are classified into two modes: the cofactor-mediated mode and the direct contact-based mode. In cofactor-mediated hybrid systems, cofactors act as reducing equivalents to shuttle electron transfer from the photocatalyst to the enzyme. In the direct-contact mode, the photocatalyst binds to the enzyme to enable direct transfer of photo-induced electrons to the catalytic active sites, or it transfers electrons to the catalytic active sites via redox active cofactors in enzymes. Besides discussing the cofactor-mediated and direct contact-based modes, a novel reaction cascade mode is reviewed. Compared to the first two modes that involve different electron transfer pathways, reaction cascades demonstrate a means to integrate photocatalysis with enzymatic catalysis by using an intermediate. This review discusses the three models in detail, the authors focus on recent advances and strategies in the construction and optimisation of the catalytic efficiency and performance of photocatalyst-enzyme hybrid systems. They also discuss the pros and cons of various photocatalysts used in hybrid systems. In particular, the progress in modifying materials to suppress electron-hole recombination and promote electrons output are reviewed. In addition, they focus on the delicate design strategies in enhancing electron transfer efficiency across the interfaces between photocatalysts and enzymes, such as integrating an electron mediator with the photocatalyst, or creating a ‘hardwire’ between the photocatalyst and the distal iron-sulphur cluster to shorten electron transfer distance. Moreover, they review the strategies used to address the incompatibility between biotic and abiotic components. Finally, for the future of this field, they provide perspective that we should focus on protecting enzymes while establishing an energy/substrate highway in the photocatalyst-enzyme hybrid, and that further development in protein engineering is also required.

This paper was published by the Institute of Food Science and Technology CAAS and Tianjin University together, and researcher Fengzhong Wang and researcher Hao Song as co-corresponding authors. The authors are grateful for the financial support from Central Public-interest Scientific Institution Basal Research Fund (Y-2017PT43-10), the National Key Research and Development Program of China (2018YFA0901300), and the National Natural Science Foundation of China (32071411, 21621004).

Scheme 1. The schematic illustration of three modes of photocatalyst-enzyme hybrid systems. Blue sector: the cofactor-mediated hybrid system. Cofactors act as reducing equivalents to shuttle electrons between photocatalysis and enzymatic catalysis. Yellow sector: the direct contact-based mode, in which photocatalysts bind with enzymes to directly transfer photo-induced electrons to the enzymes. Pink sector: the reactions cascade mode combining photocatalysis and enzymatic catalysis. The product of the first photocatalytic step will be used as a substrate (or cosubstrate) in the subsequent biocatalytic step.

Fig. 1. Carbon-derived photocatalysts used in the cofactor-mediated photocatalyst-enzyme hybrid systems. (a) Isatin and porphyrin chromophore attached graphene (CCG-IP) for M-mediated NADH cofactor regeneration upon illumination, driving the subsequent three-enzyme cascade catalysis. ET: electron transfer; M: rhodium-based complexes; FDH: formate dehydrogenase; FaldDH: formaldehyde dehydrogenase; ADH: alcohol dehydrogenase. Reproduced from (Yadav et al., 2014b), with permission from American Chemical Society. (b) Photo-excited N-doped carbon nanodots reduce mNAD+ into enzymatically active mNADH, which will donate hydride to the old yellow enzyme (OYE). Inside the OYE, FMN transfers the hydride to perform a trans-specific C– – C bond reduction. M: rhodium-based complexes; mNADH: NADH analogues; FMN: flavin mononucleotide; EWG: electron-withdrawing group. Reproduced from (Kim et al., 2018), with permission from John Wiley and Sons. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2. Dye-assemblies used in the cofactor-mediated photocatalyst-enzyme hybrid systems. (a) Chloroplast-mimicking hierarchical Cys(Zn)TPPS/ADH microspheres with two reaction centres: NAD+-dependent ADH for enzymatic NADH regeneration and Pt nanoparticles for light-driven NADH-consuming H2 production. TPPS: Tetrakis(4-sulfonatophenyl) porphine; ADH: alcohol dehydrogenase. Reproduced from (Liu et al., 2017), with permission from John Wiley and Sons. (b) An integrated photocatalyst-enzyme hybrid amyloid nanofibrils containing light-harvesting dye molecules (ThT) and redox enzymes (GDH). Photo-excited dye molecules extract electrons from TEOA to indirectly reduce NAD+ into NADH, which drives redox enzymatic reactions. ThT: Thioflavin T; GDH: L-glutamate dehydrogenase. Adapted from (Son et al., 2018b), with permission from John Wiley and Sons.

Fig. 3. Strategies for enhancing overall performance in photocatalyst-enzyme hybrid systems. (a) The concept of ‘electron buffer tank’ that coordinates the fast photophysical process (electron transfer from the photocatalyst to reaction centre) and the slow photochemical (electron utilisation: NADH regeneration) process. NH2-BDC: 2-aminoterephthalic acid. Adapted from (Wu et al., 2020), with permission from American Chemical Society. (b) The concept of ‘artificial thylakoid’. The PTi capsule wall separates the CdS QDs photosensitizer and the enzymes to avoid bioactivity loss. PTi: protamine-titania. Adapted from (Zhang et al., 2019b), with permission from American Chemical Society. (c) The M-conjugated TPE-C3N4 enhances photo-excited electron transfer and the MAF-7 MOFs protects FDH from being damaged by ROS. TPE-C3N4: thiophene-modified carbon nitride; PEI: poly(ethylenimine); MAF-7: a metal� organic framework material; FDH: formate dehydrogenase. Adapted from (Tian et al., 2020a), with permission from the American Chemical Society.

Link to the paper: https://doi.org/10.1016/j.biotechadv.2021.107808