Water-Soluble Anthraquinone Photocatalysts Enable Methanol-Driven Enzymatic Halogenation and Hydroxylation Reactions

Abstract

Peroxyzymes simply use H 2 O 2 as a cosubstrate to oxidize a broad range of inert C–H bonds. The lability of many peroxyzymes against H 2 O 2 can be addressed by a controlled supply of H 2 O 2 , ideally in situ. Here, we report a simple, robust, and water-soluble anthraquinone sulfonate (SAS) as a promising organophotocatalyst to drive both haloperoxidase-catalyzed halogenation and peroxygenase-catalyzed oxyfunctionalization reactions. Simple alcohols, methanol in particular, can be used both as a cosolvent and an electron donor for H 2 O 2 generation. Very promising turnover numbers for the biocatalysts of up to 318 000 have been achieved.

Peroxygenase-Catalyzed Selective Synthesis of Calcitriol Starting from Alfacalcidol

“…In the first set of experiments, we recombinantly produced the Pada-I variant of peroxygenase from Pichia pastoris ( Aae UPO) [ 32 ] and used alfacalcidol ( 2 ) as a model substrate to synthesize calcitriol ( 4 ). Though a number of methods for in situ provision of H 2 O 2 have been demonstrated to sustain peroxygenase [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], we chose a direct addition of H 2 O 2 via a syringe pump to simplify the reaction system. Under an arbitrarily chosen reaction condition (2.5 mM loading of 2 ), the formation of calcitriol was continuously observed over the time course as monitored by reserved phase HPLC ( Figure 2 A).…”

Methanol-Driven Oxidative Rearrangement of Biogenic Furans – Enzyme Cascades vs. Photobiocatalysis

“…Inspired by the recent reports on water-soluble anthraquinones as photoactive additives for oxygenative enzyme reactions ( Zhang et al, 2017 ; Yuan et al, 2020 ), we next replaced the oxidase/dismutase module by sodium anthraquinone-2-sulfonate (SAS) in order to create a photo-biocatalytic scenario as alternative approach, where complete oxidation of methanol to CO 2 would offer an even more elegant route. After extensive aeriation, the solutions with the yellow dye were irradiated with white LEDs.…”

“…In a first design, the chloroperoxidase-catalyzed furan oxidation was coupled to C1-active biocatalysts to arrive at a multienzymatic network for the methanol-fueled Achmatowicz reaction. For the second approach, the methanol-activating enzyme modules were replaced by a water-soluble photocatalyst ( Yuan et al, 2020 ) to create a visible light-driven process for the synthesis of the synthetically valuable, functionalized pyranone products.…”

Photo‐biocatalytic Cascades: Combining Chemical and Enzymatic Transformations Fueled by Light

“…[59] However, due to their sensitivity towards H 2 O 2 , their implementation in large-scale applications is still challenging. [59,60] Recent studies proposed the light-driven in situ generation of H 2 O 2 as a promising approach [36,[61][62][63][64][65] exhibiting improved atom efficiency compared to the conventional enzyme-catalyzed cosubstrate supply. [66] Thereby, light exposure of organic or TiO 2 -based photocatalysts in the presence of a suitable electron donor yields in the formation of photoexcited reducing equivalents, capable of the subsequent reduction of O 2 to the stoichiometric oxidant H 2 O 2 .…”