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. 2019 Jul 19;5(7):eaax0501.
doi: 10.1126/sciadv.aax0501. eCollection 2019 Jul.

Nicotinamide adenine dinucleotide as a photocatalyst

Jinhyun Kim  1 , Sahng Ha Lee  1 , Florian Tieves  2 , Caroline E Paul  2 , Frank Hollmann  2 , Chan Beum Park  1
Affiliations

Nicotinamide adenine dinucleotide as a photocatalyst

Jinhyun Kim et al. Sci Adv. .

Abstract

Nicotinamide adenine dinucleotide (NAD+) is a key redox compound in all living cells responsible for energy transduction, genomic integrity, life-span extension, and neuromodulation. Here, we report a new function of NAD+ as a molecular photocatalyst in addition to the biological roles. Our spectroscopic and electrochemical analyses reveal light absorption and electronic properties of two π-conjugated systems of NAD+. Furthermore, NAD+ exhibits a robust photostability under UV-Vis-NIR irradiation. We demonstrate photocatalytic redox reactions driven by NAD+, such as O2 reduction, H2O oxidation, and the formation of metallic nanoparticles. Beyond the traditional role of NAD+ as a cofactor in redox biocatalysis, NAD+ executes direct photoactivation of oxidoreductases through the reduction of enzyme prosthetic groups. Consequently, the synergetic integration of biocatalysis and photocatalysis using NAD+ enables solar-to-chemical conversion with the highest-ever-recorded turnover frequency and total turnover number of 1263.4 hour-1 and 1692.3, respectively, for light-driven biocatalytic trans-hydrogenation.

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Figures

Fig. 1
Fig. 1. Illustrative comparison of biological and photocatalytic functions of NAD+.
(A) Cellular NAD+ metabolism in different cellular compartments for adenosine triphosphate (ATP) synthesis, genomic integrity, mitochondrial biogenesis, improved metabolic efficiency, and life-span extension. G3PD, glyceraldehyde-3-phosphate dehydrogenase; TCA, tricarboxylic acid; ETC, electron transport chain; NAM, nicotinamide. (B) Energy diagram for NAD+-sensitized photocatalytic redox reactions [e.g., reduction of O2 to O2•−, formation of AgNPs, direct photoactivation of TsOYE (OYE homolog from Thermus scotoductus), oxidation of H2O to OH•, oxidation of MOPS, and oxidation of triethanolamine (TEOA)]. FMN, flavin mononucleotide; EWG, electron-withdrawing group.
Fig. 2
Fig. 2. NAD+-sensitized reduction of O2and oxidation of H2O.
(A) Absorbance changes of NBT solution at 560 nm with varying concentration of NAD+. ΔA(t) ≡ A(t) − A(t = 0 min). The background signal [displayed in (B)] was not subtracted from ΔA(t). Reaction condition: NAD+ and NBT in an O2-purged sodium phosphate buffer (50 mM, pH 7.5) under irradiation (xenon lamp: λ, 260 to 900 nm and P, 200 mW cm−2). (B) A series of control experiments for each reaction component (i.e., 400 μM NAD+, light, and O2) in the photochemical formation of O2•−. ΔA ≡ A(30 min) − A(0 min). Reaction conditions: NAD+ and NBT in an O2-purged sodium phosphate buffer (50 mM, pH 7.5) under irradiation (xenon lamp: λ, 260 to 900 nm and P, 200 mW cm−2). (C) Effect of NAD+ concentration on OH• formation for 30-min irradiation (200 mW cm−2). (D) Dependency of OH• formation on the light intensity (t = 30 min). Reaction conditions: 1 mM NAD+ and Tris in an O2-purged sodium phosphate buffer (50 mM, pH 7.5). All reported values represent means ± SD (n = 3).
Fig. 3
Fig. 3. NAD+-driven photocatalytic formation of AgNPs.
(A) Spectrophotometric changes in the absorbance of AgNP solution. UV-Vis absorption spectra were obtained after 10-fold dilution of samples. Inset: A photograph showing the color change of AgNP solutions containing NAD+. Photo credit: Jinhyun Kim, Korea Advanced Institute of Science and Technology. Reaction conditions: 0.5 mM NAD+ and 1 mM AgNO3 in a N2-purged MOPS buffer (50 mM, pH 7.5) under illumination (xenon lamp: P260–900 nm, 100 mW cm−2) at 293.15 K. (B) High-resolution transmission electron microscopy image of AgNPs synthesized using NAD+ for 1-min illumination. Scale bar, 20 nm. (C and D) Plausible photocatalytic cycles for the production of AgNPs driven by NAD+ through (C) an oxidative quenching process or (D) a reductive quenching process. Regardless of the processes, Ag+ ions are reduced by receiving photoexcited electrons from NAD+, whereas H2O (or MOPS) donates its electrons to NAD+.
Fig. 4
Fig. 4. Direct photoactivation of TsOYE-bound FMN using NAD+.
(A) Changes in absorbance of TsOYE-bound FMN with or without NAD+, TEOA, light, and 324-nm filter. Reaction conditions of the experimental group: 13.5 μM TsOYE, 2 mM NAD+, and 5 mM CaCl2 in N2-purged TEOA buffer (100 mM and pH 7.5). A TEOA buffer was replaced by a MOPS buffer for a control experiment. Error bars correspond to the SD (n = 3). (B) 1H nuclear magnetic resonance (NMR) spectrum of a reaction sample consisting of 2 mM NAD+ in a TEOA buffer (100 mM, pH 7.5) under illumination [xenon lamp: λ, 260 to 900 nm; P260–300 nm, 0.023 μE cm−2 s−1 (10 mW cm−2); P260–900 nm, 0.970 μE cm−2 s−1 (200 mW cm−2)] for 180 min. ppm, parts per million.
Fig. 5
Fig. 5. Hydrogenation of activated C═C bonds via direct, light-driven activation of TsOYE using NAD+.
(A) Photobiocatalytic reduction of activated C═C bonds by TsOYE. Photoactivated NAD+ transfers its photoexcited electrons to the prosthetic FMN. A substrate is trans-hydrogenated by receiving a hydride from the reduced FMN and a proton from a Tyr residue. The oxidized NAD+ returns to its initial state after receiving electrons from electron donors. (B) Time profile of the photoenzymatic reduction of 2-methyl-2-cyclohexen-1-one and enantiomeric excess (ee) of the chiral product. (C) A series of deletional control experiments. Reaction conditions of the experimental group in (B) and (C): 1.5 mM NAD+, 3 μM TsOYE, 5 mM CaCl2, and 6 mM substrate in a TEOA buffer (150 mM, pH 7.5) at 318.15 K. P260–900 nm, 1.212 μE cm−2 s−1 (250 mW cm−2). The measurement was performed in triplicate, and all reported values represent means ± SD. (D) Comparison of photobiocatalytic efficiencies for hydrogenation reaction driven by OYE. Asterisks (*) denote the approximate estimation according to data corroborated by the corresponding reference. MV, methyl viologen; TOYE, OYE from Thermoanaerobacter pseudethanolicus E39; YqjM, OYE from Bacillus subtilis.
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