Ru(II)-diimine functionalized metalloproteins: From electron transfer studies to light-driven biocatalysis

Lam, Quan; Kato, Mallory; Cheruzel, Lionel

doi:10.1016/j.bbabio.2015.09.004

Cited by 34 publications

(42 citation statements)

References 94 publications

(134 reference statements)

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“…Equally low turnover frequencies for NAD(P)H (7.4 h , displaying synthetic yields of approximately 30% in combination with a ketoreductase. Further Ru-based designs were employed for the photocatalytic activation of small molecules, such as acetylene, HCN, CO or molecular oxygen, to produce hydroxylated products 91 . Based on earlier designs, Churakova et al 92 established a photocatalytic system in combination with flavin adenine mononucleotide for an aromatic peroxidase.…”

Section: Novel Chemistries and Other Trendsmentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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N ature has evolved highly efficient systems in the form of cascade reactions, which assemble the metabolic networks that support life (growth and survival). The basic principle of cascade reactions is also frequently used in biocatalysis, using enzymes in isolation, as well as in combination with chemocatalysts (see Fig. 1 and Box 1 for definition of terms) [1][2][3][4][5][6][7] . As there is no need for purification and isolation of intermediates, operating time, production costs and waste are reduced, and concomitantly, overall yields are improved. In addition, the problem of unstable or difficult to handle intermediates can be overcome, and reactivity as well as selectivity can be enhanced by avoiding unfavourable reaction equilibria through the cooperative effects of multiple catalysts 8 . Starting in the 1980s, the early examples of the combination of chemo-and biocatalysts were reported by the van Bekkum group, who pioneered the development of a process to make the sugar substitute d-mannitol from readily available d-glucose through the combination of a heterogeneous metal-catalysed hydrogenation and an enzyme-catalysed isomerization 9 . The first broadly applied technology for the combination of enzyme and metalcatalysts, which was the research subject of many academic groups as well as industry, emerged in the 1990s from the Williams group 10,11 and aimed to achieve higher yields than classical kinetic resolution of racemates, thus overcoming the limitation of a maximum yield of 50% in the latter case. A prominent example of work that developed this theme is the combination of lipase-catalysed kinetic resolution via acylation of secondary alcohols with Pd-or Rh-catalysed racemization via reversible transfer hydrogenation to achieve a dynamic kinetic resolution (DKR) [12][13][14] . This example was facilitated in part because lipases are active and stable in organic solvents. Later, for instance, Turner's group combined a monoamine oxidase-catalysed imine formation with a chemical reduction 15 to achieve the 100% theoretical yield through a deracemization process. In addition to the combination of metalcatalysis with enzymes, organocatalysis, electrochemistry and light-induced reaction couples have since then been studied extensively, going far beyond the scope of a DKR.The challenges to combining chemo-and biocatalysis in cascades (see Box 1 for definitions and Table 1) can be daunting, not least the requirement for the chemical step to occur in the presence of water, the preferred solvent for enzymes 3 . This Review therefore highlights recent examples of the combination of chemo-and biocatalysts in aqueous multistep syntheses, and looks at how to overcome limitations by, for example, design of appropriate reaction conditions, protein engineering and advanced reactor concepts. Furthermore, trends such as the integration of transition metalcatalysis into microorganisms and the introduction of novel chemistry into engineered enzymes are discussed, and a critical assessment of the impact of this research ...

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Section: Novel Chemistries and Other Trendsmentioning

confidence: 99%

Opportunities and challenges for combining chemo- and biocatalysis

et al. 2018

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“…1 Several applications have capitalized on their photochemical properties in dye-sensitized solar cells 2 and enzymatic reactions requiring timely electron delivery. 3 …”

Section: Introductionmentioning

confidence: 99%

Correlating the para-Substituent Effects on Ru(II)-Polypyridine Photophysical Properties and on the Corresponding Hybrid P450 BM3 Enzymes Photocatalytic Activity

et al. 2017

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Ru(II)-diimine complexes covalently attached near the heme active site of P450 BM3 enzymes have been used to rapidly inject electrons and drive selective C-H functionalization upon visible light irradiation. Herein, we have generated a series of hybrid P450 BM3 enzymes containing a photosensitizer of general formula [Ru(4,4′-X2bpy)2(PhenA)]2+ where X = Cl, H, tBu, Me OPhe, OMe, or NMe2, bpy = 2, 2′-bipyridine, and PhenA = 5-acetamido-1,10-phenanthroline. We then probed the effect of electron-withdrawing and -donating groups at the para position of the 4,4′-X2bpy ligands on the corresponding hybrid enzymes photocatalytic activity. A three-fold improvement in initial reaction rate was noted when varying the substituent from Cl to tBu however, the reaction rates decrease thereafter with the more electron donating groups. In order to rationalize those effects, we investigated the variation of the substitutent on the photophysical properties of the corresponding [Ru(4,4′-X2bpy)2(bpy)]2+ model complexes. Several linear correlations were established between the E(III/II) potential, the MLCT emission and absorption energies as well as the logarithm of the luminescence quenching rate vs. the summative Brown-Okamoto parameter (Σσp+). Moreover, a downward curved Hammett plot is observed with the hybrid enzyme initial reaction rate revealing mechanistic details about the overall light-driven enzymatic process.

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“…The light-driven approach used in the hybrid P450 enzymes[5, 6, 8, 9, 15] is taking advantages of the photochemical properties of Ru(II)-diimine photosensitizers and the extensive electron transfer studies in metalloproteins. [7]…”

Section: Discussionmentioning

confidence: 99%

“…[44, 45] The X-ray structures confirm the covalent attachment of the Ru(II) photosensitizer to the non-native L407C residue as previously established using various techniques. [7] The photosensitizer resides in a bowl-shaped cavity on the proximal side of the heme domain (See Fig. 1A) where the reductase is binding.…”

Section: Discussionmentioning

confidence: 99%

“…[5, 6] This approach stems from the extensive use of these photosensitizers in long range electron transfer studies in metalloproteins and their applications in the light driven activation of small molecules with several enzymes. [7] In the hybrid P450 enzyme, the photosensitizer has been designed to deliver electrons to the heme domain upon visible light irradiation and sustain photocatalytic activity without the need for reductase and cofactor. The covalent attachment of the photosensitizer enables intramolecular electron transfers and provides control over its position relative to the heme center.…”

Section: Introductionmentioning

confidence: 99%

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Insights into an efficient light-driven hybrid P450 BM3 enzyme from crystallographic, spectroscopic and biochemical studies

Spradlin

Lee

Mahadevan

et al. 2016

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics

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Background In order to perform selective C-H functionalization upon visible light irradiation, Ru(II)-diimine functionalized P450 heme enzymes have been developed. The sL407C-1 enzyme containing the Ru(bpy)2PhenA (bpy = 2,2′-bipyridine and PhenA = 5-acetamido-1,10-phenanthroline) photosensitizer (1) covalently attached to the non-native single cysteine L407C of the P450BM3 heme domain mutant, displays high photocatalytic activity in the selective C-H bond hydroxylation of several substrates. Methods A combination of X-ray crystallography, site-directed mutagenesis, transient absorption measurements and enzymatic assays was used to gain insights into its photocatalytic activity and electron transfer pathway. Results The crystal structure of the sL407C-1 enzyme was solved in the open and closed conformations revealing a through-space electron transfer pathway involving highly conserved, F393 and Q403, residues. Several mutations of these residues (F393A, F393W or Q403W) were introduced to probe their roles in the overall reaction. Transient absorption measurements confirm rapid electron transfer as heme reduction is observed in all four hybrid enzymes. Compared to the parent sL407C-1, photocatalytic activity was negligible in the dF393A-1 enzyme while 60% increase in activity with total turnover numbers of 420 and 90% product conversion was observed with the dQ403W-1 mutant. Conclusions In the sL407C-1 enzyme, the photosensitizer is ideally located to rapidly deliver electrons, using the naturally occurring electron transfer pathway, to the heme center in order to activate molecular dioxygen and sustain photocatalytic activity. General Significance The results shed light on the design of efficient light-driven biocatalysts and the approach can be generalized to other members of the P450 superfamily.

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Ru(II)-diimine functionalized metalloproteins: From electron transfer studies to light-driven biocatalysis

Cited by 34 publications

References 94 publications

Opportunities and challenges for combining chemo- and biocatalysis

Opportunities and challenges for combining chemo- and biocatalysis

Correlating the para-Substituent Effects on Ru(II)-Polypyridine Photophysical Properties and on the Corresponding Hybrid P450 BM3 Enzymes Photocatalytic Activity

Insights into an efficient light-driven hybrid P450 BM3 enzyme from crystallographic, spectroscopic and biochemical studies

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