Biocatalytic transformation has received increasing attention in the green synthesis of chemicals because of the diversity of enzymes, their high catalytic activities and specificities, and mild reaction conditions. The idea of solar energy utilization in chemical synthesis through the combination of photocatalysis and biocatalysis provides an opportunity to make the "green" process greener. Oxidoreductases catalyze redox transformation of substrates by exchanging electrons at the enzyme's active site, often with the aid of electron mediator(s) as a counterpart. Recent progress indicates that photoinduced electron transfer using organic (or inorganic) photosensitizers can activate a wide spectrum of redox enzymes to catalyze fuel-forming reactions (e.g., H evolution, CO reduction) and synthetically useful reductions (e.g., asymmetric reduction, oxygenation, hydroxylation, epoxidation, Baeyer-Villiger oxidation). This Review provides an overview of recent advances in light-driven activation of redox enzymes through direct or indirect transfer of photoinduced electrons.

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Redox enzymes can catalyze complex synthesis reactions under mild conditions but conventional catalysts rarely accomplish this task. Despite the high potential of redox enzymes for the synthesis of valuable compounds (e.g., chiral alcohols and drug intermediates), [1][2][3][4][5] their application is hampered by the high cost of enzyme-specifi c cofactors that are required as a redox equivalent, such as nicotinamide adenine dinucleotide (NAD(P) H) and fl avin adenine dinucleotide (FADH). Thus, numerous efforts have been made over the past decades to accomplish in situ cofactor regeneration from their oxidized counterpart. [6][7][8][9] For example, researchers found that NAD(P)H can be successfully regenerated by introducing secondary enzymes [10][11][12] that reduce its oxidized counterpart (i.e., NAD(P) + ) or electrodes [13][14][15] with an external power supply into reaction media. However, these approaches present intrinsic drawbacks (e.g., by-product formation and requirement of secondary enzymes for biocatalytic regeneration, as well as extremely low yield and high overpotential for electrochemical regeneration) that hindered their practical application beyond the laboratory scale. [6][7][8] Herein, we report on the development of quantum-dotsensitized TiO 2 nanotube arrays for redox enzymatic synthesis coupled with the photoregeneration of nicotinamide cofactors via inspiration from natural photosynthesis. In natural photosynthesis, [ 16 , 17 ] incident light electronically excites a membranebound protein-pigment complexes called a photosystem. The photogenerated electrons are rapidly delivered to reaction centers along the electron transport chain for regenerating NADPH cofactors. These cofactors drive redox enzymatic reactions to synthesize organic compounds in the Calvin cycle. Its unique features (e.g., environmental compatibility and nearunity quantum yield) have fascinated scientists and provided inspiration to improve the effi ciency of solar cells and photoelectrochemical hydrogen production systems. [18][19][20][21][22][23][24] In the present study, the photosystem for in situ NAD(P)H regeneration consisted of TiO 2 -CdS nanotubes as a photoelectrode, triethanolamine (TEOA) as an electron donor, and pentamethylcyclopentadienyl rhodium bipyridine ([Cp * Rh(bpy)(H 2 O)] 2 + ) as an electron mediator and a hydride transfer catalyst ( Figure S1, Supporting Information). As a photoelectrode for non-enzymatic regeneration of NAD(P)H, a nanotubular TiO 2 -CdS fi lm has many advantages that include easy synthesis and morphology control, [ 25 , 26 ] effi cient charge separation, [ 24 , 27 ] and better diffusion of reaction species through nanotube channels. Due to the small size and more negative position of the conduction band (CB) edge of CdS compared to TiO 2 (at least 0.2 V more negative), photogenerated electrons can be rapidly injected from CdS to TiO 2 in a thermodynamically favorable manner ( Figure S1, Supporting Information). This injection suppresses electron-hole recombination, which is more...

In green plants, solar-energy utilization is accomplished through a cascade of photoinduced electron transfer, which remains a target model for realizing artificial photosynthesis. We introduce the concept of biocatalyzed artificial photosynthesis through coupling redox biocatalysis with photocatalysis to mimic natural photosynthesis based on visible-light-driven regeneration of enzyme cofactors. Key design principles for reaction components, such as electron donors, photosensitizers, and electron mediators, are described for artificial photosynthesis involving biocatalytic assemblies. Recent research outcomes that serve as a proof of the concept are summarized and current issues are discussed to provide a future perspective.

Light-driven activation of redox enzymes is an emerging route for sustainable chemical synthesis. Among redox enzymes, the family of Old Yellow Enzyme (OYE) dependent on the nicotinamide adenine dinucleotide cofactor (NADH) catalyzes the stereoselective reduction of α,β-unsaturated hydrocarbons. Here, we report OYE-catalyzed asymmetric hydrogenation through light-driven regeneration of NADH and its analogues (mNADHs) by N-doped carbon nanodots (N-CDs), a zero-dimensional photocatalyst. Our spectroscopic and photoelectrochemical analyses verified the transfer of photo-induced electrons from N-CDs to an organometallic electron mediator (M) for highly regioselective regeneration of cofactors. Light triggered the reduction of NAD and mNAD s with the cooperation of N-CDs and M, and the reduction behaviors of cofactors were dependent on their own reduction peak potentials. The regenerated cofactors subsequently delivered hydrides to OYE for stereoselective conversions of a broad range of substrates with excellent biocatalytic efficiencies.

Redox enzymes catalyze fascinating chemical reactions with excellent regio- and stereo-specificity. Nicotinamide adenine dinucleotide cofactor is essential in numerous redox biocatalytic reactions and needs to be regenerated because it is consumed as an equivalent during the enzymatic turnover. Here we report on unbiased photoelectrochemical tandem assembly of a photoanode (FeOOH/BiVO4) and a perovskite photovoltaic to provide sufficient potential for cofactor-dependent biocatalytic reactions. We obtain a high faradaic efficiency of 96.2% and an initial conversion rate of 2.4 mM h−1 without an external applied bias for the photoelectrochemical enzymatic conversion of α-ketoglutarate to l-glutamate via l-glutamate dehydrogenase. In addition, we achieve a total turnover number and a turnover frequency of the enzyme of 108,800 and 6200 h−1, respectively, demonstrating that the tandem configuration facilitates redox biocatalysis using light as the only energy source.

Cytochromes P450 can catalyze various regioselective and stereospecific oxidation reactions of non-functionalized hydrocarbons. Here, we have designed a novel light-driven platform for cofactor-free, whole-cell P450 photo-biocatalysis using eosin Y (EY) as a photosensitizer. EY can easily enter into the cytoplasm of Escherichia coli and bind specifically to the heme domain of P450. The catalytic turnover of P450 was mediated through the direct transfer of photoinduced electrons from the photosensitized EY to the P450 heme domain under visible light illumination. The photoactivation of the P450 catalytic cycle in the absence of cofactors and redox partners is successfully conducted using many bacterial P450s (variants of P450 BM3) and human P450s (CYPs 1A1, 1A2, 1B1, 2A6, 2E1, and 3A4) for the bioconversion of different substrates, including marketed drugs (simvastatin, lovastatin, and omeprazole) and a steroid (17β-estradiol), to demonstrate the general applicability of the light-driven, cofactor-free system.

Dye-sensitized photosynthesis: Eosin Y (EY), a dye photosensitizer, works efficiently as a molecular photoelectrode by catalyzing the visible-light-driven electron-transfer reaction for efficient regeneration of NADH through a photosensitizer-electron relay dyad. Injection of the photosensitized electron resulted in highly accelerated regeneration of NADH, which can be used by glutamate dehydrogenase for the photosynthesis of L-glutamate.