Received: 29 January 2023 | Revised: 27 February 2023 | Accepted: 13 March 2023 DOI: 10.1002/bit.28383 REVIEW Application of gas diffusion electrodes in bioeconomy: An update Markus Stöckl1 | Thomas Lange2 | Paniz Izadi3 | Sera Bolat2 | Niklas Teetz2 | Falk Harnisch3 | Dirk Holtmann2 1 DECHEMA Research Institute, Sustainable Electrochemistry, Frankfurt am Main, Abstract Germany The transition of today's fossil fuel based chemical industry toward sustainable 2 Institute of Bioprocess Engineering and Pharmaceutical Technology, University of production requires improvement of established production processes as well as Applied Sciences Mittelhessen, Giessen, development of new sustainable and bio‐based synthesis routes within a circular Germany economy. Thereby, the combination of electrochemical and biotechnological 3 Department of Environmental Microbiology, UFZ—Helmholtz‐Centre for Environmental advantages in such routes represents one important keystone. For the Research GmbH, Leipzig, Germany electrochemical generation of reactants from gaseous substrates such as O2 or CO2, gas diffusion electrodes (GDE) represent the electrodes of choice since they Correspondence Dirk Holtmann, Institute of Bioprocess overcome solubility‐based mass transport limitations. Within this article, we Engineering and Pharmaceutical Technology, illustrate the architecture, function principle and fabrication of GDE. We highlight University of Applied Sciences Mittelhessen, Wiesenstrasse 14, 35390 Giessen, Germany. the application of GDE for conversion of CO2 using abiotic catalysts for subsequent Email: dirk.holtmann@lse.thm.de biosynthesis as well as the application of microbial catalysts at GDE for CO2 Funding information conversion. The reduction of oxygen at GDE is summarized for the application of Deutsche Forschungsgemeinschaft; oxygen depolarized cathodes in microbial fuel cells and generation of H2O2 to drive Helmholtz Association; European Union's Horizon 2020, Grant/Award Number: enzymatic reactions. Finally, engineering aspects such as scale‐up and the modeling 101000441; German Federal Ministry of of GDE‐based processes are described. This review presents an update on the Economic Affairs and Climate Action; Bundesministerium für Bildung und application of GDE in bio‐based production systems and emphasizes their large Forschung, Grant/Award Numbers: potential for sustainable development of new pathways in bioeconomy. 33RC031A, 33RC031B, 33RC031E KEYWORDS bioeconomy, C1‐biotechnology, CO2 conversion, electrobiotechnology, gas diffusion electrode, hydrogen peroxide dependent enzymes 1 | INTRODUCTION selectivity of the biocatalysts is combined with a high energy efficiency of the electrochemical reaction step. Common examples The combination of electrochemical and microbial as well as enzymatic are the electrochemical substitution or regeneration of cofactors reactions is well‐established in the field of biosensors (Bedendi (Castañeda‐Losada et al., 2021; Çekiç et al., 2010; Dong et al., 2020; et al., 2022). In bioeconomy in general, this combination is believed El Housseini et al., 2021; Tosstorff et al., 2014; Xu et al., 2021; to be highly effective to optimize established processes or to setup Yuan et al., 2019; C. Zhang et al., 2022) and the electrochemical new production routes (Harnisch & Urban, 2018). Often, the high generation of reactants for biotransformations (Haas et al., 2018; This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC. Biotechnol Bioeng. 2023;120:1465–1477. wileyonlinelibrary.com/journal/bit | 1465 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1466 | STÖCKL ET AL. Hegner et al., 2020; Horst, Bormann, et al., 2016; Kracke et al., 2021; for the reduction of CO2 to CO and formate or O2 to H2O or H2O2. Krieg et al., 2018; Stöckl et al., 2020; Teetz et al., 2022; Tremblay Driven by the generally low solubility of gases in aqueous reaction et al., 2019). High Technology Readiness Levels (TRL) and high systems, GDE were invented and designed to circumvent this intrinsic relevance to achieve the Sustainable Development Goals of the United mass transport limitation (Hernandez‐Aldave & Andreoli, 2020; S. Lu Nations were demonstrated, especially for the electrochemical et al., 2022). In 2016 we summarized the application of GDE for production of reactants and the subsequent microbial and enzymatic biosynthesis using enzymatic and microbial energy conversions conversion (Fruehauf et al., 2020; Stöckl et al., 2022). Different (Horst, Mangold, et al., 2016). In the last years, the application fields processes are now transitioning from well‐characterized conditions of GDE in biotechnology have been significantly expanded, calling for and optimized reaction systems in the laboratory setting toward this update. realization of technical production sites with similar performance GDE are based on nano‐porous materials which serve as a three‐ indicators (e.g., Haas et al., 2018; Kopljar et al., 2016). The phase interphase between a gas, a liquid and a solid electrocatalyst. development toward technical scale is a grand challenge and hence Through the combination of different materials, GDE provide three‐ scaling‐up is increasingly becoming a focus of research. To realize high dimensional hydrophilic and hydrophobic networks, which enable the productivity and energy efficiencies, three main issues must be electrochemical conversion of gases by circumventing their low addressed: (i) high mass transport, (ii) large specific electrode area solubility in an aqueous electrolyte solution. A schematic of a cross per volume (Ae; ratio between the electrode surface and the reaction section of a GDE is presented in Figure 1. Technically, formation of volume), and (iii) high reaction selectivity. In “classical” electrochemical hydrophobic and hydrophilic regions inside the GDE is realized by engineering, targeting abiotic reactions only, technical electrolysis combining hydrophobic materials such as polytetrafluoroethylene cells with three‐dimensional electrodes are well established. These (PTFE) with hydrophilic and electric conductivity increasing additives electrochemical cells provide an enlarged specific electrode area and such as carbon‐based materials and electrocatalysts. The hydropho- improved mass transport due to the specific fluid dynamics bic PTFE allows the formation of a porous three‐dimensional gas inside the three‐dimensional electrode structure. Typical examples of passage network throughout the GDE. The remaining components, such three‐dimensional reaction systems are porous flow‐through such as carbon‐based additives and electrocatalyst materials, form reactors, packed‐ and fluidized bed cells and gas diffusion electrode hydrophilic pores, which allow a transport of electrolyte solution (GDE) designed setups. To generate reactants for subsequent inside the GDE. Under ideal operation conditions (pressure equili- biotransformations, gaseous substrates are often reduced, exemplarily, brium between gas and liquid), the GDE is partially flooded with gas F I G U R E 1 Schematic cross section illustration of a gas diffusion electrodes (GDE). Description from left to right: gas phase; porous GDE system comprised of a current collector (current collector mesh schematically illustrated as a cross section of single metal mesh fibers) and electrocatalyst particles. A curved pattern inside the GDE schematically shows the vertical pattern of the 3‐phase boundary, electrolyte solution at the right side of the GDE. Insert: schematic of the 3‐phase boundary, where the gas phase, the liquid electrolyte phase and the solid electrocatalyst phase are in direct contact. Exemplarily, the cathodic hydrogen peroxide synthesis from oxygen is shown. 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1467 and electrolyte solution, respectively, which leads to the formation of The eCO2RR to CO at GDE gained an increasing interest in the three‐phase boundaries inside the GDE (see insert in Figure 1), where scientific and industrial communities within the last decade since process the gas phase, the aqueous phase and the solid electrocatalyst phase performance parameters point toward promising commercialization are in direct contact with each other. This allows the electrocatalytic (Masel et al., 2021). Typical catalysts for CO generation are silver (Ag) conversion of gases with solutes on one moiety, regardless of the (Kim et al., 2016), gold (Au) (Verma et al., 2018), and platinum (Pt) (Du solubility of the gas in the electrolyte solution. The architecture of et al., 2013), (see Table 2). Thereby the most applied electrocatalyst GDE depends on the fabrication method and on the size of the GDE. material for CO formation by eCO2RR by far is Ag due to its high Small‐scale (up to few cm2) GDE are often comprised of a layered selectivity for CO, relatively high abundance and comparably low price design, where the electrocatalyst is applied on a hydrophobic (Enzmann et al., 2022). Kutz et al. achieved high FE of 96.9% at (carbon‐based) gas diffusion layer, for example, by spraying of an −100 mA cm−2 and outstanding long‐term performance of several 1000 h ink, which contains the catalyst or its precursor. Usually, PTFE and an with Ag‐based carbon GDE (Kutz et al., 2017). This was accomplished by ionomer (e.g., Nafion®) are part of the catalyst ink to adjust the using an imidazolium functionalized styrene vinylbenzyl chloride co‐ hydrophobicity of the catalyst layer and transport, respectively. polymer as an anion exchange membrane. Further optimization was Large‐scale electrodes such as silver‐based oxygen depolarization realized by adding porous carbon and imidazolium functionalized electrodes or carbon black‐based GDE for H2O2 synthesis are monomer to an Ag‐containing ink used to spray paint onto the carbon composed of mechanically stabilizing and current collecting metal support (Liu et al., 2018). The optimized Ag‐based carbon GDE cathode grids (Figure 1) and the hydrophobic, conducting and electrocatalytic could be operated at −200 mA cm−2, a cell voltage of 3 V, and a CO materials. Usually, the respective materials are provided as a selectivity of 98%. Dinh et al. used an Ag‐coated porous PTFE membrane homogenous particle mixture and are combined with the current being spray coated with carbon as a current collector and compared the collector mesh under pressure and increased temperature (e.g., via CO2 reduction to CO at different pH (Dinh et al., 2018). They achieved FE calendering) to prepare the GDE (Bidault et al., 2009). to CO of more than 90% at current densities of more than −150 mA cm−2 in neutral and alkaline electrolyte solutions and longtime stability of more than 100 h. The gaseous electrolysis‐originating CO stream can be 2 | C ONVER SION OF CO 2 A T G D E U S IN G combined with hydrogen produced via water electrolysis to obtain syngas ABIOTIC CATALYSTS (CO and H2 mixture) serving as a sustainable feedstock for a biotechnological process, as illustrated in Figure 2b. Both gaseous The electrochemical conversion of CO2 is considered as one of the products can be generated separately or simultaneously within the same most promising strategies for converting CO2 into value‐added electrolysis set‐up (co‐electrolysis) to directly achieve syngas. The chemicals. For the realization of CO2‐based industrial processes, the respective co‐electrolysis has been demonstrated by Haas and co‐ electrochemical conversion should present high product concentra- workers with Ag‐based electrodes from Covestro (Haas et al., 2018), tions, productivities, current densities and long‐term operation achieving a stable syngas production throughout more than 1000 h at a stabilities. Furthermore, high Faradaic efficiencies (FE; indicates the high current density of −300 mA cm−2 with constant cell voltage within amount/ratio of current/electrons, which participate in the electro- 7.0–7.5 V. Furthermore, using a mixed culture of Clostridium autoethano- chemical target reaction; also referred as coulombic efficiency and genum and Clostridium kluyveri, they impressively demonstrated the sometimes current efficiency, CE) are desired to minimize the fraction production of butanol and hexanol directly from electrolysis‐originating of electrochemical by‐ and/or side‐products. Electrocatalysts for the syngas in a separate bioreactor. selective electrochemical reduction of CO2 and the underlying Similar attempts to optimize the overall process can be seen for the reaction mechanism have been intensely researched in the last electrochemical CO2 reduction to formic acid/formate, even though the decades. Table 1 summarizes the currently most important and TRL is currently not as high as it is for the eCO2RR to CO. Like CO promising electrochemical CO2 reduction reactions (eCO2RR) to synthesis, the eCO2RR to formic acid/formate requires two electrons produce possible feedstock for subsequent bioprocesses. (Table 1). The most widely used electrocatalysts are tin (Sn) or tin oxide (SnOx) (Löwe et al., 2021) and modified Sn‐based materials (Lin et al., 2022). Other reported selective catalysts are indium (In) (Bitar T A B L E 1 Electrochemical reactions, number of transferred et al., 2016; Hegner et al., 2018), amalgams (Park & Shin, 2021) and electrons (z) and standard equilibrium potentials (E°) at pH = 0 for the bismuth‐based materials (García de Arquer et al., 2018; Wang et al., 2021), CO2 conversion to biotechnological relevant products (Kortlever whereby the latter shows increased catalysts stability toward alkaline et al., 2015). catalyst corrosion (Bienen et al., 2021). In a comprehensive and well‐ Product Reaction z E0 vs. RHE structured review, Han and co‐workers summarized the achievements on Carbon + − CO2 + 2H3O + 2e → CO + 3H2O 2 −0.10 V metal‐based nano‐structured electrocatalysts for formate synthesis (Han monoxide et al., 2020). For instance, with a three‐compartment electrolyzer using an Formic acid − CO2 + 2H3O + 2e → HCOOH + 2H2O 2 −0.20 V + imidazole functionalized Sustainion™ membrane technology, Yang and co‐workers produced formic acid directly with 5–20 wt%, high FE and Methanol CO2 + 6H3O+ + 6 e− → CH3OH + 5H2O 6 0.02 V current densities at Sn‐based GDE (H. Yang et al., 2017). After further 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1468 | STÖCKL ET AL. TABLE 2 Examples of the commonly used catalysts in GDE for the CO2 reduction to CO and Formate. Active center/electro Current density Faraday catalysts Support material Main product [mA cm−2] efficiency [%] Literature Au Carbon CO 158 99 Verma et al. (2018) Ag GDE/XA‐9 ionomer CO 200 98 Liu et al. (2018) Ni Carbon substrate CO 308.4 88 H. Yang, Lin, et al. (2020) − Sn PTFE + Carbon HCOO 400 75 Kopljar et al. (2016) − Bi Carbon substrate HCOO 200 90 García de Arquer et al. (2018) Sn PTFE + Carbon HCOO− 800 85 Löwe et al. (2019) − Sn Carbon + PTFE + Nafion HCOO 1800 70 Löwe et al. (2021) F I G U R E 2 Schematic illustration of different applications of gas diffusion electrodes (GDE) in bioeconomy. GDE is illustrated by porous black electrode of the respective schemes. Oxygen evolution reaction is displayed as anodic counter reaction, except for scheme E. (a) CO2 reduction with abiotic electrocatalysts to formate (COOH−) coupled with a formate‐based fermentation to bio‐products (P). (b) Co‐electrolysis of CO2 and water with abiotic electrocatalysts to obtain carbon monoxide and hydrogen gas mixture (CO + H2), which is fed to a syngas‐based fermentation. (c) CO2 conversion with microbial catalysts. Microbial catalysts displayed as GDE associated biofilm and planktonic cells. (d) Oxygen reduction for hydrogen peroxide (H2O2) synthesis, which is subsequently consumed enzymatically for product generation. (e) Oxygen reduction at oxygen depolarization electrodes to water as cathodic counter reaction for the microbially catalyzed wastewater oxidation in microbial fuel cells. 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1469 optimization, they yielded a long‐term stability of 1000 h at 200 mA cm−2, able to wire their metabolisms to an electron flow at the electrode which titers of 1.3–2.8 M formic acid, depending on operational (Schröder et al., 2015; Sydow et al., 2014). This concept of MES is conditions (H. Yang, Lin, et al., 2020). In contrast to the syngas‐based also denominated as a primary microbial electrochemical technology processes (Figure 2b), formic acid/formate represents a less toxic and (MET) and has to be distinguished from approaches using a secondary liquid/solid feedstock, which can be beneficial in terms of feedstock MET. Secondary MET approaches are based on abiotic electrocata- storage and process safety. The respective eCO2RR to formate at GDE lysis and indirectly connected to microbial synthesis, for example, by for providing microbial feedstock combined with the biosynthesis is the electrochemical generation of feedstock (see above) (Izadi & displayed in Figure 2a. A perspective on the use of formate as sole carbon Harnisch, 2022; Schröder et al., 2015). For MES in primary MET, source for the production of value‐added chemicals has been published the GDE design aims to allow sufficient supply of CO2 for the by Yishai and co‐workers (Yishai et al., 2016). Exemplarily, the formate‐ microorganisms. Further, it shall provide the suitable interface based bioproduction with formate originating from the eCO2RR at Sn‐ between the gas and cathode solution for the biofilm formation at based GDE has been demonstrated to produce the polymer polyhydroxy the electrode surface, where CO2 enters the cathodic compartment. butyrate (PHB) by Cupriavidus necator. Furthermore, the formate‐ Only few studies have exploited GDE for MES, and in most it remains containing electrolyte was used as a biological feedstock without any uncertain, whether the microbial electrocatalysts reduce CO2 directly intermediate purification step respectively downstream processing or use electrochemical hydrogen generated at the cathode as a (Stöckl et al., 2020). mediator/reducing agent. This is probably due to the challenges As mentioned before, the eCO2RR to CO and formic acid/ involved in controlling the microbial activities in such complex reactor formate at GDE represent processes to provide sustainable feedstock designs compared to conventional reactor setups like H‐cells or for biosynthesis. However, both feedstocks come with a relatively stirred tank reactors. One of the first studies on MES using GDE was low energy content (high degree of reduction), which either requires reported by Bajracharya et al (Bajracharya et al., 2016). In this study, a high substrate‐to‐product ratio or limits the product spectrum of a GDE reactor using a porous activated carbon electrode was the bioprocess. Therefore, eCO2RR products of higher energy/ inoculated with a mixed microbial culture and operated at the electron content, such as alcohols, represent a desirable sustainable cathodic potential of −1.1 V versus Ag/AgCl using a circular Pt sheet feedstock from the mid‐ to long‐term perspective since they can be as a counter electrode. The inoculum was assumed to be dominated used in already established processes such as methanol‐based by homoacetogenic bacteria after a four‐stage enrichment from a biotechnology (Schrader et al., 2009; Singh et al., 2022; W. Zhang wastewater sludge (including heating the sludge, heterotrophic and et al., 2018). The synthesis of alcohols by eCO2RR requires the autotrophic growth, followed by four autotrophic growth transfers) transfer of multiple electrons, and the selectivity to alcohols is (Mohanakrishna et al., 2015). The authors discussed the faster CO2 generally much lower than that to CO, formic acid and even ethylene. mass transfer in the GDE setup compared to the conventional CO2 Currently, developments on the selective eCO2RR to alcohols such as sparging reactor, and therefore the higher production rate. Mass methanol are on a low TRL and reviewed by Al‐Rowaili and co‐ transfer coefficient for CO2 in the reactor with a GDE was estimated workers (Al‐Rowaili et al., 2018). Reported catalysts for the methanol almost two times higher than that in the reactor with a sparger synthesis are based on copper (Cu) (Azenha et al., 2020; Hazarika & (estimated mass transfer coefficient of 3.92 compared to 1.81 per h), Manna, 2019; L. Lu et al., 2018; D. Yang et al., 2019; H. Yang leading to maximum CO2 transfer rates of 91 mg L−1 min−1 and et al., 2019), cobalt (Co) (Wu et al., 2019) or boron phosphide 42 mg L−1 min−1 (at 25°C), respectively. Detecting acetate as the main materials (Mou et al., 2019). So far, the results reported for alcohol and ethanol and butyrate as the secondary products, the maximum synthesis via eCO2RR are very promising in terms of selectivity and acetate production rate in this study was 238 mg L−1 d−1. Afterwards, show increasing current densities. However, catalyst and/or elec- Srikanth et al. studied a similar setup for MES from CO2 using a trode stabilities are not comparable with CO and formic acid/formate microbial mixed culture (Srikanth et al., 2018). As the pH was not electrodes, and the transfer from dispersed electrodes and catalyst controlled during the 90 days of experiment and due to the development to GDE (Azenha et al., 2020) is often unpredictable and accumulation of formate and acetate, more diverse compounds such currently on an early development stage. Thus, intensive academia as ethanol, butyrate and butanol were produced. Overall production and industry‐driven research is required to successfully apply GDE rates of 233 mg L−1 d−1 alcohols and 144 mg L−1 d−1 organic acids for alcohol synthesis via eCO2RR for biological feedstocks and to were reported. The effect of three different flow rates of CO2 (5, 10, close the gaps between both processes (Stöckl et al., 2022). and 20 mL min−1) was also compared in both H‐cells and GDE reactors using mixed population of microorganisms (Rojas et al., 2021). Although increase in the flow rate of gaseous CO2 improved the 3 | C ONVER SION OF CO 2 A T G D E U S IN G acetate production rate in the H‐cell reaching a maximum value of M I C R O B I A L CA T A L Y S T S 270 mg L−1 d−1, the lower CO2 flow rate allowed the higher gas‐liquid transfer in the GDE reactors. As a result, the highest acetate Conversion of CO2 to value‐added chemicals can also be achieved by production rate (85 mg L−1 d−1) in the GDE reactors was achieved at using microbial electrocatalysts which is called microbial electro- the lowest CO2 flow rate (5 mL min−1). In addition, Fontmorin et al. synthesis (MES) (Figure 2c). These electroactive microorganisms are reported the modification of a GDE using binary‐doped polyaniline 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1470 | STÖCKL ET AL. polymer (Fontmorin et al., 2021). The key role of microbial biofilms As mentioned before, GDE are often used as cathodes for the formed at the cathode for MES from CO2 was previously shown ORR to water in MFC, (Figure 2e). The major reason is the need of a (Izadi et al., 2020). Following that, Fontmorin et al. showed the effect cathode in MFC that does not limit the microbially catalyzed anodic of polyaniline polymer on increasing the hydrophilicity and bio- reactions, like it is often found with non‐gas diffusion cathodes (Rossi compatibility of the electrode, leading to a rapid biofilm formation et al., 2019). GDE‐based MFC (also known as air cathode MFC) have from the mixed population of microorganisms at the GDE for been shown to be a suitable configuration to overcome limitations eCO2RR. As a result, faster start‐up and higher production of acetate due to oxygen solubility. This is particularly advantageous when and subsequently butyrate was observed. The authors showed the microorganisms catalyze ORR, as one of the key factors controlling increase in acetate and butyrate production rates from maximum 17 the performance of aerobic biocathodes was shown to be the mass and 1 mg L−1 d−1 when a plain carbon GDE was used to maximum 183 transfer of O2 (Ter Heijne et al., 2010). In addition, GDE design −1 −1 and 6 mg L d when using a polymer coating with polyaniline at the discards the need for a constant aeration using an air pump, which is GDE, respectively. Although not many studies focused on MES by an economic burden (Rossi et al., 2022). Previously, air cathode MFC primary MET using GDE, in all available studies the GDE design were used in different research fields such as COD removal increased the production when compared to conventional setups. (X. Zhang et al., 2015), monitoring of water or wastewater quality (Di Lorenzo et al., 2014; Holtmann & Sell, 2002), wastewater treatment (Feng et al., 2008; Sevda et al., 2013), and so forth, and 4 | R E D U C T IO N OF OX Y G E N AT to improve reactor designs (Fan et al., 2007; You et al., 2007). Only G DE —O X Y G E N C A T H O DE S A ND TH E few studies have evaluated the performance of MFC based on gas GENERA TION OF H 2 O 2 diffusion cathodes using microbial catalysts for ORR. Xia et al. studied the development of biocathodes in a GDE reactor, which was initially The oxygen reduction reactions (ORR) are important cathode enriched in a dual chamber electrochemical cell (Xia et al., 2013). reactions for the synthesis of chemicals and energy storage (e.g., Additionally, the authors discussed the higher maximum current proton exchange membrane fuel cells or metal‐air batteries). density generated in the air cathode MFC with biocathode (1 A m−2) Depending on the pH, the electrolyte composition, the electro- than that generated in the dual chamber MFC (0.49 A m−2). Izadi et al. catalyst, the applied potential and further parameters, different also studied the MFC with iron‐oxidizing bacteria (IOB) as a reactions take place (Table 3). The 4‐electron reduction pathway biocathode enriched from iron‐rich river sediment using a GDE (Izadi from O2 to H2O is often used as cathode reaction in microbial fuel et al., 2019). After developing the biocathode in the GDE setup under cells (MFC, Figure 2e). Here, the main advantages are the harmless 3‐electrode configuration, the authors discussed that GDE was reaction product water as well as the high potential difference responsible for regeneration of ferrous ion required as an energy between the anode and the cathode making the MFC a source of source for IOB, which provided constant available oxygen needed for electric power. In electroenzymatic processes, the 2‐electron reduc- their metabolisms. Using the developed biocathode in an air cathode tion pathway is used to produce hydrogen peroxide as reactant for MFC led to maximum power of 1100 mW m−2. This result was higher H2O2‐dependent enzymes ([Burek et al., 2019], [Figure 2d]). This than the maximum power produced in the similar MFC, but with a Pt 2‐electron reduction also occurs as a side reaction of the 4‐electron (5 mg cm−2) coated GDE, which was 500 mW m−2. Apart from the pathway, leading to a decrease in performance of the MFC (Zhao aforementioned reports, the majority of studies on GDE used abiotic et al., 2006). Typical electrocatalysts for the 4‐electron pathway are electrocatalysts in MFC. Platinised graphite paper GDE was one of Pt and further elements from the Pt‐group. In the last decade, the common electrode materials used for ORR in GDE designed MFC significant achievements have been made to use non‐Pt group previously, for example, (Cheng et al., 2006; Logan et al., 2007). elements (e.g., [Shao et al., 2016; Tian et al., 2020]). The most However, over the past decade several studies focused on the common electrocatalyst for the production of H2O2 is carbon development of different electrocatalysts suitable for GDE reactors. material in various configurations and modifications (Rozendal For instance, stainless‐steel mesh and a cobalt oxide hybrid electrode et al., 2009). (Gong et al., 2014) were utilized to achieve a stable and efficient ORR T A B L E 3 Products, electrochemical reactions, number of transferred electrons (z) and potentials for the reduction of O2 at different pH (selected examples, [Senarathna et al., 2016]). Reaction product(s) and condition Reaction z E vs. SHE Water, acidic electrolyte solution (pH = 0, [H+(aq)] = 1 mol L) O2 + 4H+ + 4e− → 2H2O 4 1.229 V Hydrogen peroxide, acidic electrolyte (pH = 0, [H+(aq)] = 1 mol L) solution O2 + 2H+ + 2e− → H2O2 2 0.670 V − − − Hydroxide ion, alkaline electrolyte solution (pH = 14, [OH (aq)] = 1 mol L) O2 + 4e + 2H2O → 4OH 4 0.401 V − − Hydroxide ion + hydroperoxyl, alkaline electrolyte (pH = 14, [OH (aq)] = 1 mol L) solution O2 + 2e + H2O → HO2− + OH− 2 −0.065 V 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1471 to improve the MFC performance (Carrillo‐Rodríguez et al., 2019; large capabilities provided by optimized electrodes have already been Santoro et al., 2016; Srikanth et al., 2016). used to decrease overpotentials. The coating of a GDE with oxidized As mentioned before, hydrogen peroxide (H2O2) can be carbon nanotubes can lead to a decreased overpotential by around generated in a 2‐electron reduction of oxygen and subsequently 100 mV, compared to unmodified electrodes, during ORR to H2O2 applied in enzymatic processes with H2O2‐dependent enzymes (Bormann et al., 2019). Recently, a process model was introduced (Figure 2d). In these processes, H2O2 acts as a co‐substrate for a which allows to predict optimized reaction conditions of electro- wide range of enzymatic reactions (e.g., hydroxylations, epoxidations, enzymatic processes with H2O2‐dependend enzymes (Bormann sulfoxidations, halogenations, Baeyer–Villiger oxidations, decarbox- et al., 2021). The developed model can also be used for efficient ylations) (Burek et al., 2019). However, in addition to serving as a co‐ process development with different enzymes. Furthermore, the use substrate, the H2O2 could also show negative effect on the enzyme of GDE in electroenzymatic processes was extended further. stability. In particular, heme‐dependent peroxidases and peroxy- Schuhmann and co‐workers modified a GDE with a viologen‐based genases tend to irreversible oxidative inactivation by H2O2. This redox polymer and tungsten dependent formate dehydrogenase effect was investigated in detail by using the heme‐containing (Szczesny et al., 2020). This system was used to produce formate chloroperoxidase from Caldariomyces fumago (CfuCPO). While the from CO2. theoretical ratio of H2O2 to the substrate monochlorodimedone is A further future‐oriented combination is the use of a cathodic 1:1, it has been shown that the highest operational stability is hydrogen peroxide‐producing GDE and an anodic microbial fuel cell achieved at a ratio of 0.1:1 (Holtmann et al., 2014). This indicates that in wastewater treatment (Rozendal et al., 2009; Sim et al., 2018). In high enzyme stabilities can preferentially be achieved in a hydrogen such microbial electrolysis cells (MECs) the anodic conversion of peroxide limited process. One major challenge in the technical organic wastewater components provides the majority of energy for application of the H2O2‐dependent enzymes is to control the H2O2 the cathodic conversion of O2 to H2O2. H2O2‐producing MECs can concentration at levels that enable efficient catalytic turnover of the yield significant profits over other MECs due to high cost and enzyme while simultaneously minimizing the undesired inactivation demand of hydrogen peroxide (Sim et al., 2018). reaction (Burek et al., 2019). Besides other supply methods, the electrochemical in‐situ generation of H2O2 in scalable reactors was evaluated as an energy and resource efficient process (Bormann 5 | E N G I N E E R I N G AS P E C T S— SCAL E‐U P et al., 2019, 2021; Getrey et al., 2014; Holtmann et al., 2014; Horst, A N D MO D E L I N G OF G D E‐B A S E D Bormann, et al., 2016; Krieg et al., 2011; Lütz et al., 2007). Lütz et al PRO CESS ES used a fixed bed electrode and the CfuCPO to oxidize thioanisole to (R)‐methylphenylsulfoxide (Lütz et al., 2007). GDE‐based reactors As demonstrated, the majority of GDE‐based processes are showing were used as an alternative concept to fixed bed electrodes. High promising key performance indicators. The next step toward oxygen concentration next to the catalyst improved mass transfer in industrial realization is now to increase the scale and especially the electrode, high specific electrode surface areas and the avoidance overall production volume of the processes. While “conventional” of gassing the reactor are claimed to be the main advantages. Table 4 bioprocesses are typically volume dependent, electrobiotechnological shows different electroenzymatic processes based on hydrogen processes are in first instance surface‐dependent (Enzmann peroxide dependent enzymes and GDE. The aim of most of these et al., 2019). This scale‐up challenge is reduced in the case of the studies was to improve the operational stability of the enzymes and GDE‐based processes, as here the reactants are mostly generated to broaden the product portfolio. The FE depend on the applied electrochemically in the electrode while the subsequent biological electrolyte/buffer system. The measured FE in sodium acetate buffer reaction takes place in the reactor volume. The technical realization (pH 5.0) with addition of 50 mM sodium sulfate or 100 mM citrate of a large scale GDE‐based process was demonstrated for the abiotic buffer (pH 2.75) with addition of 10 mM sodium chloride as electrochemical chlorine production (press release from thyssenk- electrolyte were 88 ± 4% and 55%, respectively (Krieg et al., 2011). rupp Uhde and Bayer MaterialScience from June 2013, [Moussallem Organic co‐solvents are often used to realize sufficient concentration et al., 2008]). The specific challenge in electrobiotechnology will be to of hydrophobic substrates in enzymatic reactions. By using a buffer adapt requirements and performances of the respective electro- containing 100 mM potassium phosphate (pH 7.0) and 3% acetone, chemical and microbial or enzymatic processes to each other. In the FE was approx. Seventy‐one percent (Horst, Bormann, particular, model‐based approaches can be used for both a et al., 2016). One particular challenge when using organic solvents knowledge‐based design of the individual steps as well as for a is the hydrophilicity of the GDE. Hydrophobic solvents and conceptual design of the overall processes. As most prominent substrates can prevent establishing a proper 3‐phase boundary example, Able and Clark developed a multiphysics model to analyze a between the electrolyte solution, electrocatalyst and the gas phase. formate‐mediated microbial electrosynthesis with the aerobic Furthermore, leakage problems could occur (Getrey et al., 2014; “Knallgas” bacteria Cupriavidus necator (Abel & Clark, 2021). The Horst, Bormann, et al., 2016). These effects can only be addressed by comprehensive model includes transport phenomena, electrochemi- electrode engineering. This has only been done to a small extent, as in cal and microbial reactions, thermodynamic and kinetic effects, most investigations commercial electrodes were used. However, the temperature effects, and gas/liquid mass transfer. This showed that | 1472 T A B L E 4 Electrochemical reactions, number of transferred electrons and standard potentials for reduction of O2 (selected examples, ttn = total turnover number, ratio between the total moles of product yield per mole of added biocatalyst). Enzyme Enzymatic conversion Reaction conditions Key performance indicators Literature −1 −1 Heme‐containing Thioanisole to methyl phenyl sulfoxide 100 or 600 nM CfuCPO, 100 mM sodium acetate ttnEnzyme = 83,600, productivity 19.8 g L d Krieg chloroperoxidase from buffer pH 5 + 50 mM Na2SO4, carbon‐based (100 nM enzyme and 1.8 mA cm−2), et al. (2011) Caldariomyces fumago commercial GDE, 16.5 cm2,a, 1.8 or 5.5 mA cm−2 ttnEnzyme = 3120, productivity 23 g L−1 d−1 (CfuCPO) (600 nM enzyme and 5.5 mA cm−2) CfuCPO Indole to oxindole 100 nM CfuCPO, 100 mM ttnEnzyme = 39,000, productivity 8.3 g L−1 d−1 Krieg citrate buffer pH 2.75 + 10 mM NaCl, carbon‐based et al. (2011) commercial GDE, 16.5 cm2,a, 1.8 mA cm−2 CfuCPO Monochlorodimedone (MCD, 5–30 nM CfuCPO, 100 mM citrate buffer ttnEnzyme = 1,150,000 Holtmann surrogate substrate) to pH 2.75/3.5, carbon‐based commercial GDE, et al. (2014) dichlorodimedone 5.5 cm2,a, 2.7–5.5 mA cm−2 CfuCPO Thymol to chlorothymol 100 nM CfuCPO, 100 mM citrate buffer + 50 mM Productivity 20.4 g L−1 d−1 Getrey NaCl, pH 3.5, carbon‐based commercial GDE, et al. (2014) 5.5 cm2,a, 8.2 mA cm−2 Recombinant unspecific Ethylbenzene to 1‐phenethyl alcohol 50 nM rAaeUPO, 100 mM potassium phosphate ttn = 400,000 (at 10 mA cm−2), productivity Horst, Bormann, peroxygenase from Agrocybe buffer pH 25 g L−1 d−1 (at 25 mA cm−2) et al. (2016) aegerita (rAaeUPO) 7.0 + 3% acetone as second phase, carbon‐based commercial GDE, 2 cm2,a, 5−30 mA cm−2 Vanadium chloroperoxidase from 4‐Pentenoic acid to bromolactone 100 nM CiVCPO, 100 mM sodium citrate (pH 5) Productivity 3.4 g L−1 d−1 Bormann Curvularia inaequalis (CiVCPO) with 100 mM KBr, GDE modified with oxidized et al. (2019) carbon nanotubes (oCNTs), 4.5 cm2,a, −0.35 V versus Ag/AgCl rAaeUPO 4‐ethylbenzoic acid to 4‐(1‐Hydroxy‐ 12.5 nM rAaeUPO, 100 mM potassium phosphate ttn approx. 400,000 (at 1.8 mA cm−2), turnover Bormann ethyl)benzoic acid buffer pH frequency up to 135 s−1 (at 10.9 mA cm−2) et al. (2021) 7.0, carbon‐based commercial GDE, 5.5 cm2,a, 1.8–14.5 mA cm−2 a Geometrical surface. STÖCKL ET AL. 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1473 formate‐mediated microbial electrosynthesis reactors needed for this review: All authors. Preparation of tables and figures, and validation of specific bacterium are mainly limited by the trade‐off between O2 the manuscript: All authors gas/liquid mass transfer and CO2 transport to the cathode surface (Abel & Clark, 2021). They concluded that the decoupling of the ACKNOWLEDGME NT S electrochemical and microbial processes into separate reactors This research is financed by the German Federal Ministry of overcomes this limitation. Further modeling includes for example, Education and Research (BMBF) under the GAMES project (Grant the model‐based improvement of GDE (Heßelmann et al., 2022), nr: 33RC031A; 33RC031B; 33RC031E). The authors also acknowl- model‐based upscaling of GDE based CO2‐reduction systems (Z. edge the support of the VIVALDI project that has received funding Yang et al., 2021) and a multi‐criteria optimization of H2O2 synthesis from the European Union's Horizon 2020 research and innovation in GDE (von Kurnatowski & Bortz, 2021). program under grant agreement 101000441. Further acknowledg- ment goes to the German Federal Ministry of Economic Affairs and Climate Action (Grant nr: 21866 N‐1). Parts of this work was funded 6 | C ONC LUSION AND OUTLOOK by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—465474720. This work was also supported by the For improvement of established production processes as well as Helmholtz‐Association in the frame of the Integration Platform development of new sustainable and biobased synthesis routes “Tapping nature's potential for sustainable production and a healthy within a circular economy, the combination of biotechnology and environment” at the UFZ. Open Access funding enabled and electrochemistry is a powerful tool. Whenever electrochemically or organized by Projekt DEAL. electromicrobially catalyzed (cathodic) reactions involve the con- sumption of gaseous compounds, applying GDE can significantly DATA AVAILABILITY STATEMENT improve the overall process, since GDE circumvent the poor solubility The data that support the findings of this study are available from the of gases in aqueous and biocompatible electrolyte solution. GDE are corresponding author upon reasonable request. the electrode of choice for the eCO2RR to different carbon‐based chemicals, which can be used as a sustainable feedstock for ORC I D biotechnological synthesis. Especially for syngas‐based fermenta- Dirk Holtmann http://orcid.org/0000-0001-5540-3550 tions, this elegant coupling of electrochemical CO2 fixation to CO and microbial synthesis is currently in the transition to larger‐scale RE F ER EN CES industrial realization (press release from the companies Evonik and Abel, A. J., & Clark, D. S. (2021). A comprehensive modeling analysis of Siemens, from October 10, 2019). Although not many studies formate‐mediated microbial electrosynthesis**. Chemsuschem, 14(1), 344–355. https://doi.org/10.1002/cssc.202002079 focused on MES in primary MET using GDE, in all available studies Al‐Rowaili, F. N., Jamal, A., Ba Shammakh, M. S., & Rana, A. (2018). A the GDE design showed improved production compared to conven- review on recent advances for electrochemical reduction of carbon tional setups. In H2O2‐dependent enzyme‐based systems, GDE were dioxide to methanol using metal–organic framework (MOF) and non‐ successfully used for the energy and resource‐efficient in‐situ H2O2 MOF catalysts: Challenges and future prospects. ACS Sustainable Chemistry & Engineering, 6(12), 15895–15914. https://doi.org/10. production from O2 at levels that enable efficient catalytic turnover 1021/acssuschemeng.8b03843 of the enzyme while simultaneously minimizing the undesired Azenha, C., Mateos‐Pedrero, C., Alvarez‐Guerra, M., Irabien, A., & inactivation reaction. Mendes, A. (2020). Enhancement of the electrochemical reduction This wide variety of applications shows that GDE are one of the of CO2 to methanol and suppression of H2 evolution over CuO nanowires. Electrochimica Acta, 363, 137207. https://doi.org/10. key engineering components for the successful electrification of 1016/j.electacta.2020.137207 the bioeconomy (Harnisch & Urban, 2018). In both academic Bajracharya, S., Vanbroekhoven, K., Buisman, C. J. N., Pant, D., & research and industry‐driven biobased process development, Strik, D. P. B. T. B. (2016). Application of gas diffusion biocathode GDE engineering provides the possibility to enhance the conver- in microbial electrosynthesis from carbon dioxide. Environmental Science and Pollution Research, 23(22), 22292–22308. sion of gaseous feedstock sustainably and significantly. The Bedendi, G., De Moura Torquato, L. D., Webb, S., Cadoux, C., Kulkarni, A., development of GDE and their application in the bioeconomy is Sahin, S., Maroni, P., Milton, R. D., & Grattieri, M. (2022). Enzymatic an ongoing process, involving for instance electrode and process and microbial electrochemistry: Approaches and methods. ACS scale‐up, process and electrode stability and reaction design for the Measurement Science Au, 2(6), 517–541. https://doi.org/10.1021/ acsmeasuresciau.2c00042 integration and interconnection of electrochemical and biobased Bidault, F., Brett, D. J. L., Middleton, P. H., & Brandon, N. P. (2009). reactions (Harnisch & Holtmann, 2019). Review of gas diffusion cathodes for alkaline fuel cells. Journal of Power Sources, 187(1), 39–48. https://doi.org/10.1016/j.jpowsour. A U T H O R C O N TR I B U T I O N S 2008.10.106 Bienen, F., Löwe, A., Hildebrand, J., Hertle, S., Schonvogel, D., Kopljar, D., Conceptualization of the review, supervision, and funding acquisition: Wagner, N., Klemm, E., & Friedrich, K. A. (2021). Degradation study Markus Stöckl and Falk Harnisch und Dirk Holtmann. Contribution to on tin‐ and bismuth‐based gas‐diffusion electrodes during electro- the concept: All authors. Literature mining: All authors. Writing of the chemical CO2 reduction in highly alkaline media. Journal of Energy 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1474 | STÖCKL ET AL. Chemistry, 62, 367–376. https://doi.org/10.1016/j.jechem.2021. feedstocks for sustainable bioproduction (pp. 213–241). Springer 03.050 International Publishing. https://doi.org/10.1007/10_2021_171 Bitar, Z., Fecant, A., Trela‐Baudot, E., Chardon‐Noblat, S., & Pasquier, D. Enzmann, F., Stöckl, M., Zeng, A.‐P., & Holtmann, D. (2019). Same but (2016). Electrocatalytic reduction of carbon dioxide on indium different–scale up and numbering up in electrobiotechnology and coated gas diffusion electrodes—Comparison with indium foil. photobiotechnology. Engineering in Life Sciences, 19(2), 121–132. Applied Catalysis, B: Environmental, 189, 172–180. https://doi.org/ https://doi.org/10.1002/elsc.201800160 10.1016/j.apcatb.2016.02.041 Fan, Y., Hu, H., & Liu, H. (2007). Enhanced coulombic efficiency and power Bormann, S., Hertweck, D., Schneider, S., Bloh, J. Z., Ulber, R., Spiess, A. C., density of air‐cathode microbial fuel cells with an improved cell & Holtmann, D. (2021). Modeling and simulation‐based design of configuration. Journal of Power Sources, 171(2), 348–354. electroenzymatic batch processes catalyzed by unspecific peroxygen- Feng, Y., Wang, X., Logan, B. E., & Lee, H. (2008). Brewery wastewater ase from A. Aegerita. Biotechnology and Bioengineering, 118(1), 7–16. treatment using air‐cathode microbial fuel cells. Applied Microbiology https://doi.org/10.1002/bit.27545 and Biotechnology, 78(5), 873–880. Bormann, S., Schie, M. M. C. H., De Almeida, T. P., Zhang, W., Stöckl, M., Fontmorin, J.‐M., Izadi, P., Li, D., Lim, S. S., Farooq, S., Bilal, S. S., Ulber, R., Hollmann, F., & Holtmann, D. (2019). H2O2 production at Cheng, S., & Yu, E. H. (2021). Gas diffusion electrodes modified with low overpotentials for electroenzymatic halogenation reactions. binary doped polyaniline for enhanced CO2 conversion during Chemsuschem, 12(21), 4759–4763. https://doi.org/10.1002/cssc. microbial electrosynthesis. Electrochimica Acta, 372, 137853. 201902326 Fruehauf, H. M., Enzmann, F., Harnisch, F., Ulber, R., & Holtmann, D. Burek, B. O., Bormann, S., Hollmann, F., Bloh, J. Z., & Holtmann, D. (2019). (2020). Microbial electrosynthesis—An inventory on technology Hydrogen peroxide driven biocatalysis. Green Chemistry, 21(12), readiness level and performance of different process variants. 3232–3249. https://doi.org/10.1039/C9GC00633H Biotechnology Journal, 15(10), 2000066. https://doi.org/10.1002/ Carrillo‐Rodríguez, J. C., García‐Mayagoitia, S., Pérez‐Hernández, R., biot.202000066 Ochoa‐Lara, M. T., Espinosa‐Magaña, F., Fernández‐Luqueño, F., García de Arquer, F. P., Bushuyev, O. S., De Luna, P., Dinh, C.‐T., Bartolo‐Pérez, P., Alonso‐Lemus, I. L., & Rodríguez‐Varela, F. J. Seifitokaldani, A., Saidaminov, M. I., Tan, C.‐S., Quan, L. N., (2019). Evaluation of the novel PdCeO2‐NR electrocatalyst sup- Proppe, A., Kibria, M. G., Kelley, S. O., Sinton, D., & Sargent, E. H. ported on N‐doped graphene for the oxygen reduction reaction and (2018). 2D metal oxyhalide‐derived catalysts for efficient CO2 its use in a microbial fuel cell. Journal of Power Sources, 414, electroreduction. Advanced Materials, 30(38), 1802858. https://doi. 103–114. org/10.1002/adma.201802858 Castañeda‐Losada, L., Adam, D., Paczia, N., Buesen, D., Steffler, F., Getrey, L., Krieg, T., Hollmann, F., Schrader, J., & Holtmann, D. (2014). Sieber, V., Erb, T. J., Richter, M., & Plumeré, N. (2021). Bioelec- Enzymatic halogenation of the phenolic monoterpenes thymol and trocatalytic cofactor regeneration coupled to CO2 fixation in a carvacrol with chloroperoxidase. Green Chemistry, 16(3), 1104–1108. redox‐active hydrogel for stereoselective C−C bond formation. https://doi.org/10.1039/C3GC42269K Angewandte Chemie International Edition, 60(38), 21056–21061. Gong, X.‐B., You, S.‐J., Wang, X.‐H., Zhang, J.‐N., Gan, Y., & Ren, N.‐Q. https://doi.org/10.1002/anie.202103634 (2014). A novel stainless steel mesh/cobalt oxide hybrid electrode Çekiç, S. Z., Holtmann, D., Güven, G., Mangold, K.‐M., Schwaneberg, U., & for efficient catalysis of oxygen reduction in a microbial fuel cell. Schrader, J. (2010). Mediated electron transfer with P450cin. Biosensors and Bioelectronics, 55, 237–241. Electrochemistry Communications, 12(11), 1547–1550. https://doi. Haas, T., Krause, R., Weber, R., Demler, M., & Schmid, G. (2018). Technical org/10.1016/j.elecom.2010.08.030 photosynthesis involving CO2 electrolysis and fermentation. Nature Cheng, S., Liu, H., & Logan, B. E. (2006). Increased performance of single‐ Catalysis, 1(1), 32–39. https://doi.org/10.1038/s41929-017-0005-1 chamber microbial fuel cells using an improved cathode structure. Han, N., Ding, P., He, L., Li, Y., & Li, Y. (2020). Promises of main group Electrochemistry Communications, 8(3), 489–494. metal–based nanostructured materials for electrochemical CO2 Dinh, C.‐T., García de Arquer, F. P., Sinton, D., & Sargent, E. H. (2018). reduction to formate. Advanced Energy Materials, 10(11), 1902338. High rate, selective, and stable electroreduction of CO2 to CO in https://doi.org/10.1002/aenm.201902338 basic and neutral media. ACS Energy Letters, 3(11), 2835–2840. Harnisch, F., & Urban, C. (2018). Electrobiorefineries: Unlocking the https://doi.org/10.1021/acsenergylett.8b01734 synergy of electrochemical and microbial conversions. Angewandte Di Lorenzo, M., Thomson, A. R., Schneider, K., Cameron, P. J., & Chemie International Edition, 57(32), 10016–10023. https://doi.org/ Ieropoulos, I. (2014). A small‐scale air‐cathode microbial fuel cell 10.1002/anie.201711727 for on‐line monitoring of water quality. Biosensors and Bioelectronics, Harnisch, F. H., & Dirk, H. (2019). Bioelectrosynthesis. Springer Nature. 62, 182–188. Hazarika, J., & Manna, M. S. (2019). Electrochemical reduction of CO2 to Dong, F., Chen, H., Malapit, C. A., Prater, M. B., Li, M., Yuan, M., Lim, K., & methanol with synthesized Cu2O nanocatalyst: Study of the Minteer, S. D. (2020). Biphasic bioelectrocatalytic synthesis of chiral selectivity. Electrochimica Acta, 328, 135053. https://doi.org/10. β‐hydroxy nitriles. Journal of the American Chemical Society, 142(18), 1016/j.electacta.2019.135053 8374–8382. https://doi.org/10.1021/jacs.0c01890 Hegner, R., Neubert, K., Kroner, C., Holtmann, D., & Harnisch, F. (2020). Du, C., Chen, M., Wang, W., Tan, Q., Xiong, K., & Yin, G. (2013). Platinum‐ Coupled electrochemical and microbial catalysis for the production based intermetallic nanotubes with a core–shell structure as highly of polymer bricks. Chemsuschem, 13(19), 5295–5300. https://doi. active and durable catalysts for fuel cell applications. Journal of org/10.1002/cssc.202001272 Power Sources, 240, 630–635. https://doi.org/10.1016/j.jpowsour. Hegner, R., Rosa, L. F. M., & Harnisch, F. (2018). Electrochemical CO2 2013.05.023 reduction to formate at indium electrodes with high efficiency and El Housseini, W., Lapicque, F., Walcarius, A., & Etienne, M. (2021). A hybrid selectivity in pH neutral electrolytes. Applied Catalysis, B: electrochemical flow reactor to couple H2 oxidation to NADH Environmental, 238, 546–556. https://doi.org/10.1016/j.apcatb. regeneration for biochemical reactions. Electrochemical Science 2018.07.030 Advances, 2(4), e202100012. https://doi.org/10.1002/elsa.202100012 Hernandez‐Aldave, S., & Andreoli, E. (2020). Fundamentals of gas Enzmann, F., Stöckl, M., Pfitzer, M., & Holtmann, D. (2022). Empower C1: diffusion electrodes and electrolysers for carbon dioxide utilisation: Combination of electrochemistry and biology to convert C1 Challenges and opportunities. Catalysts, 10(6), 713. https://www. compounds. In A.‐P. Zeng & N. J. Claassens (Eds.), One‐carbon mdpi.com/2073-4344/10/6/713 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1475 Heßelmann, M., Bräsel, B. C., Keller, R. G., & Wessling, M. (2022). Lin, C., Xu, Z., Kong, X., Zheng, H., Geng, Z., & Zeng, J. (2022). Lysine‐ Simulation‐based guidance for improving CO2 reduction on silver functionalized SnO2 for efficient CO2 electroreduction into formate. gas diffusion electrodes. Electrochemical Science Advances, 3(1), ChemNanoMat, 8(5), e202200020. https://doi.org/10.1002/cnma. 2100160. https://doi.org/10.1002/elsa.202100160 202200020 Holtmann, D., Krieg, T., Getrey, L., & Schrader, J. (2014). Electroenzymatic Liu, Z., Yang, H., Kutz, R., & Masel, R. I. (2018). CO2 electrolysis to CO and process to overcome enzyme instabilities. Catalysis Communications, O2 at high selectivity, stability and efficiency using sustainion 51, 82–85. https://doi.org/10.1016/j.catcom.2014.03.033 membranes. Journal of the Electrochemical Society, 165(15), Holtmann, D., & Sell, D. (2002). Detection of the microbial activity of J3371–J3377. https://doi.org/10.1149/2.0501815jes aerobic heterotrophic, anoxic heterotrophic and aerobic autotrophic Logan, B., Cheng, S., Watson, V., & Estadt, G. (2007). Graphite fiber brush activated sludge organisms with an electrochemical sensor. anodes for increased power production in air‐cathode microbial fuel Biotechnology Letters, 24(16), 1313–1318. https://doi.org/10. cells. Environmental Science & Technology, 41(9), 3341–3346. 1023/A:1019871912731 Löwe, A., Rieg, C., Hierlemann, T., Salas, N., Kopljar, D., Wagner, N., & Horst, A. E. W., Bormann, S., Meyer, J., Steinhagen, M., Ludwig, R., Klemm, E. (2019). Influence of temperature on the performance of Drews, A., Ansorge‐Schumacher, M., & Holtmann, D. (2016). gas diffusion electrodes in the CO2 reduction reaction. Electro‐enzymatic hydroxylation of ethylbenzene by the evolved ChemElectroChem, 6(17), 4497–4506. https://doi.org/10.1002/celc. unspecific peroxygenase of Agrocybe aegerita. Journal of Molecular 201900872 Catalysis B: Enzymatic, 133, S137–S142. https://doi.org/10.1016/j. Löwe, A., Schmidt, M., Bienen, F., Kopljar, D., Wagner, N., & Klemm, E. molcatb.2016.12.008 (2021). Optimizing reaction conditions and gas diffusion electrodes Horst, A. E. W., Mangold, K.‐M., & Holtmann, D. (2016). Application of gas applied in the CO2 reduction reaction to formate to reach current diffusion electrodes in bioelectrochemical syntheses and energy densities up to 1.8 A cm–2. ACS Sustainable Chemistry & Engineering, conversion. Biotechnology and Bioengineering, 113(2), 260–267. 9(11), 4213–4223. https://doi.org/10.1021/acssuschemeng.1c00199 https://doi.org/10.1002/bit.25698 Lu, L., Sun, X., Ma, J., Yang, D., Wu, H., Zhang, B., Zhang, J., & Han, B. Izadi, P., Fontmorin, J.‐M., Fernández, L. F. L., Cheng, S., Head, I., & Yu, E. H. (2018). Highly efficient electroreduction of CO2 to methanol on (2019). High performing gas diffusion biocathode for microbial fuel Palladium–Copper bimetallic aerogels. Angewandte Chemie cells using acidophilic iron oxidizing bacteria. Frontiers in Energy International Edition, 57(43), 14149–14153. https://doi.org/10. Research, 7, 93. https://doi.org/10.3389/fenrg.2019.00093 1002/anie.201808964 Izadi, P., Fontmorin, J.‐M., Godain, A., Yu, E. H., & Head, I. M. (2020). Lu, S., Wang, Y., Xiang, H., Lei, H., Xu, B. B., Xing, L., Yu, E. H., & Liu, T. X. Parameters influencing the development of highly conductive and (2022). Mass transfer effect to electrochemical reduction of CO2: efficient biofilm during microbial electrosynthesis: The importance of Electrode, electrocatalyst and electrolyte. Journal of Energy Storage, applied potential and inorganic carbon source. NPJ Biofilms and 52, 104764. https://doi.org/10.1016/j.est.2022.104764 Microbiomes, 6(1), 40. Lütz, S., Vuorilehto, K., & Liese, A. (2007). Process development for the Izadi, P., & Harnisch, F. (2022). Microbial| electrochemical CO2 reduction: electroenzymatic synthesis of (R)‐methylphenylsulfoxide by use of a To integrate or not to integrate? Joule, 6(5), 935–940. 3‐dimensional electrode. Biotechnology and Bioengineering, 98(3), Kim, B., Hillman, F., Ariyoshi, M., Fujikawa, S., & Kenis, P. J. A. (2016). 525–534. https://doi.org/10.1002/bit.21434 Effects of composition of the micro porous layer and the substrate Masel, R. I., Liu, Z., Yang, H., Kaczur, J. J., Carrillo, D., Ren, S., Salvatore, D., & on performance in the electrochemical reduction of CO2 to CO. Berlinguette, C. P. (2021). An industrial perspective on catalysts for Journal of Power Sources, 312, 192–198. https://doi.org/10.1016/j. low‐temperature CO2 electrolysis. Nature Nanotechnology, 16(2), jpowsour.2016.02.043 118–128. https://doi.org/10.1038/s41565-020-00823-x Kopljar, D., Wagner, N., & Klemm, E. (2016). Transferring electrochemical Mohanakrishna, G., Seelam, J. S., Vanbroekhoven, K., & Pant, D. (2015). CO2 reduction from semi‐batch into continuous operation mode An enriched electroactive homoacetogenic biocathode for the using gas diffusion electrodes. Chemical Engineering & Technology, microbial electrosynthesis of acetate through carbon dioxide 39(11), 2042–2050. https://doi.org/10.1002/ceat.201600198 reduction. Faraday Discussions, 183, 445–462. Kortlever, R., Shen, J., Schouten, K. J. P., Calle‐Vallejo, F., & Mou, S., Wu, T., Xie, J., Zhang, Y., Ji, L., Huang, H., Wang, T., Luo, Y., Koper, M. T. M. (2015). Catalysts and reaction pathways for the Xiong, X., Tang, B., & Sun, X. (2019). Boron phosphide nanoparticles: electrochemical reduction of carbon dioxide. The Journal of Physical A nonmetal catalyst for high‐selectivity electrochemical reduction of Chemistry Letters, 6(20), 4073–4082. https://doi.org/10.1021/acs. CO2 to CH3OH. Advanced Materials, 31(36), 1903499. https://doi. jpclett.5b01559 org/10.1002/adma.201903499 Kracke, F., Deutzmann, J. S., Jayathilake, B. S., Pang, S. H., Moussallem, I., Jörissen, J., Kunz, U., Pinnow, S., & Turek, T. (2008). Chlor‐ Chandrasekaran, S., Baker, S. E., & Spormann, A. M. (2021). Efficient alkali electrolysis with oxygen depolarized cathodes: History, present hydrogen delivery for microbial electrosynthesis via 3D‐printed status and future prospects. Journal of Applied Electrochemistry, 38(9), cathodes. Frontiers in Microbiology, 12, 1. https://doi.org/10.3389/ 1177–1194. https://doi.org/10.1007/s10800-008-9556-9 fmicb.2021.696473 Park, M., & Shin, W. (2021). Long‐term stable and selective conversion of Krieg, T., Hüttmann, S., Mangold, K.‐M., Schrader, J., & Holtmann, D. carbon dioxide to formate using dental amalgam electrode. Journal of (2011). Gas diffusion electrode as novel reaction system for an CO2 Utilization, 45, 101435. https://doi.org/10.1016/j.jcou.2021. electro‐enzymatic process with chloroperoxidase. Green Chemistry, 101435 13(10), 2686–2689. https://doi.org/10.1039/C1GC15391A Rojas, M. P. A., Zaiat, M., González, E. R., De Wever, H., & Pant, D. (2021). Krieg, T., Sydow, A., Faust, S., Huth, I., & Holtmann, D. (2018). CO2 to Enhancing the gas–liquid mass transfer during microbial electro- terpenes: Autotrophic and electroautotrophic α‐humulene production synthesis by the variation of CO2 flow rate. Process Biochemistry, with cupriavidus necator. Angewandte Chemie International Edition, 101, 50–58. 57(7), 1879–1882. https://doi.org/10.1002/anie.201711302 Rossi, R., Hur, A. Y., Page, M. A., Thomas, A. O., Butkiewicz, J. J., Kutz, R. B., Chen, Q., Yang, H., Sajjad, S. D., Liu, Z., & Masel, I. R. (2017). Jones, D. W., Baek, G., Saikaly, P. E., Cropek, D. M., & Logan, B. E. Sustainion imidazolium‐functionalized polymers for carbon dioxide (2022). Pilot scale microbial fuel cells using air cathodes for electrolysis. Energy Technology, 5(6), 929–936. https://doi.org/10. producing electricity while treating wastewater. Water Research, 1002/ente.201600636 215, 118208. 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 1476 | STÖCKL ET AL. Rossi, R., Wang, X., Yang, W., & Logan, B. E. (2019). Impact of cleaning Teetz, N., Holtmann, D., Harnisch, F., & Stöckl, M. (2022). Upgrading procedures on restoring cathode performance for microbial fuel cells Kolbe electrolysis—Highly efficient production of green fuels and treating domestic wastewater. Bioresource Technology, 290, 121759. solvents by coupling biosynthesis and electrosynthesis. Angewandte Rozendal, R. A., Leone, E., Keller, J., & Rabaey, K. (2009). Efficient Chemie International Edition, 61(50), e202210596. https://doi.org/ hydrogen peroxide generation from organic matter in a bioelec- 10.1002/anie.202210596 trochemical system. Electrochemistry Communications, 11(9), Ter Heijne, A., Strik, D. P., Hamelers, H. V., & Buisman, C. J. (2010). 1752–1755. https://doi.org/10.1016/j.elecom.2009.07.008 Cathode potential and mass transfer determine performance of Santoro, C., Serov, A., Stariha, L., Kodali, M., Gordon, J., Babanova, S., oxygen reducing biocathodes in microbial fuel cells. Environmental Bretschger, O., Artyushkova, K., & Atanassov, P. (2016). Iron based Science & Technology, 44(18), 7151–7156. catalysts from novel low‐cost organic precursors for enhanced Tian, X., Lu, X. F., Xia, B. Y., & Lou, X. W. (2020). Advanced electrocatalysts oxygen reduction reaction in neutral media microbial fuel cells. for the oxygen reduction reaction in energy conversion technologies. Energy & Environmental Science, 9(7), 2346–2353. Joule, 4(1), 45–68. https://doi.org/10.1016/j.joule.2019.12.014 Schrader, J., Schilling, M., Holtmann, D., Sell, D., Filho, M. V., Marx, A., & Tosstorff, A., Dennig, A., Ruff, A. J., Schwaneberg, U., Sieber, V., Vorholt, J. A. (2009). Methanol‐based industrial biotechnology: Mangold, K.‐M., Schrader, J., & Holtmann, D. (2014). Mediated Current status and future perspectives of methylotrophic bacteria. electron transfer with monooxygenases—Insight in interactions Trends in Biotechnology, 27(2), 107–115. https://doi.org/10.1016/j. between reduced mediators and the co‐substrate oxygen. Journal tibtech.2008.10.009 of Molecular Catalysis B: Enzymatic, 108, 51–58. https://doi.org/10. Schröder, U., Harnisch, F., & Angenent, L. T. (2015). Microbial electro- 1016/j.molcatb.2014.06.011 chemistry and technology: Terminology and classification. Energy & Tremblay, P.‐L., Faraghiparapari, N., & Zhang, T. (2019). Accelerated H2 Environmental Science, 8(2), 513–519. evolution during microbial electrosynthesis with sporomusa ovata. Senarathna, K. G. C., Randiligama, H. M. S. P., & Rajapakse, R. M. G. (2016). Catalysts, 9(2), 166. https://doi.org/10.3390/catal9020166 Preparation, characterization and oxygen reduction catalytic activities Verma, S., Hamasaki, Y., Kim, C., Huang, W., Lu, S., Jhong, H.‐R. M., of nanocomposites of Co(ii)/montmorillonite containing polypyrrole, Gewirth, A. A., Fujigaya, T., Nakashima, N., & Kenis, P. J. A. (2018). polyaniline or poly(ethylenedioxythiophene). RSC Advances, 6(114), Insights into the low overpotential electroreduction of CO2 to CO on a 112853–112863. https://doi.org/10.1039/C6RA23100D supported gold catalyst in an alkaline flow electrolyzer. ACS Energy Sevda, S., Dominguez‐Benetton, X., Vanbroekhoven, K., De Wever, H., Letters, 3(1), 193–198. https://doi.org/10.1021/acsenergylett.7b01096 Sreekrishnan, T. R., & Pant, D. (2013). High strength wastewater von Kurnatowski, M., & Bortz, M. (2021). Modeling and multi‐criteria treatment accompanied by power generation using air cathode optimization of a process for H2O2 electrosynthesis. Processes, 9(2), microbial fuel cell. Applied Energy, 105, 194–206. 399. Shao, M., Chang, Q., Dodelet, J.‐P., & Chenitz, R. (2016). Recent advances Wang, Y., Li, Y., Liu, J., Dong, C., Xiao, C., Cheng, L., Jiang, H., Jiang, H., & in electrocatalysts for oxygen reduction reaction. Chemical Reviews, Li, C. (2021). BiPO4‐derived 2D nanosheets for efficient electro- 116(6), 3594–3657. https://doi.org/10.1021/acs.chemrev.5b00462 catalytic reduction of CO2 to liquid fuel. Angewandte Chemie Sim, J., Reid, R., Hussain, A., An, J., & Lee, H.‐S. (2018). Hydrogen peroxide International Edition, 60(14), 7681–7685. https://doi.org/10.1002/ production in a pilot‐scale microbial electrolysis cell. Biotechnology anie.202014341 Reports, 19, e00276. https://doi.org/10.1016/j.btre.2018.e00276 Wu, Y., Jiang, Z., Lu, X., Liang, Y., & Wang, H. (2019). Domino Singh, H. B., Kang, M. K., Kwon, M., & Kim, S. W. (2022). Developing electroreduction of CO2 to methanol on a molecular catalyst. methylotrophic microbial platforms for a methanol‐based bioindus- Nature, 575(7784), 639–642. https://doi.org/10.1038/s41586-019- try. Frontiers in Bioengineering and Biotechnology, 10, 1050740. 1760-8 https://doi.org/10.3389/fbioe.2022.1050740 Xia, X., Tokash, J. C., Zhang, F., Liang, P., Huang, X., & Logan, B. E. (2013). Srikanth, S., Pant, D., Dominguez‐Benetton, X., Genné, I., Vanbroekhoven, K., Oxygen‐reducing biocathodes operating with passive oxygen trans- Vermeiren, P., & Alvarez‐Gallego, Y. (2016). Gas diffusion electrodes fer in microbial fuel cells. Environmental Science & Technology, 47(4), manufactured by casting evaluation as air cathodes for microbial fuel 2085–2091. cells (MFC). Materials, 9(7), 601. Xu, K., Chatzitakis, A., Backe, P. H., Ruan, Q., Tang, J., Rise, F., Bjørås, M., & Srikanth, S., Singh, D., Vanbroekhoven, K., Pant, D., Kumar, M., Puri, S. K., & Norby, T. (2021). In situ cofactor regeneration enables selective CO2 Ramakumar, S. S. V. (2018). Electro‐biocatalytic conversion of carbon reduction in a stable and efficient enzymatic photoelectrochemical dioxide to alcohols using gas diffusion electrode. Bioresource cell. Applied Catalysis, B: Environmental, 296, 120349. https://doi. Technology, 265, 45–51. org/10.1016/j.apcatb.2021.120349 Stöckl, M., Claassens, N., Lindner, S., Klemm, E., & Holtmann, D. (2022). Yang, D., Zhu, Q., Chen, C., Liu, H., Liu, Z., Zhao, Z., Zhang, X., Liu, S., & Coupling electrochemical CO2 reduction to microbial product Han, B. (2019). Selective electroreduction of carbon dioxide to generation— Identification of the gaps and opportunities. Current methanol on copper selenide nanocatalysts. Nature Communications, Opinion in Biotechnology, 74, 154–163. https://doi.org/10.1016/j. 10(1), 677. https://doi.org/10.1038/s41467-019-08653-9 copbio.2021.11.007 Yang, H., Kaczur, J. J., Sajjad, S. D., & Masel, R. I. (2017). Electrochemical Stöckl, M., Harms, S., Dinges, I., Dimitrova, S., & Holtmann, D. (2020). conversion of CO2 to formic acid utilizing Sustainion™ membranes. From CO2 to bioplastic—Coupling the electrochemical CO2 reduc- Journal of CO2 Utilization, 20, 208–217. https://doi.org/10.1016/j. tion with a microbial product generation by drop‐in electrolysis. jcou.2017.04.011 Chemsuschem, 13(16), 4086–4093. https://doi.org/10.1002/cssc. Yang, H., Lin, Q., Zhang, C., Yu, X., Cheng, Z., Li, G., Hu, Q., Ren, X., 202001235 Zhang, Q., Liu, J., & He, C. (2020). Carbon dioxide electroreduction Sydow, A., Krieg, T., Mayer, F., Schrader, J., & Holtmann, D. (2014). on single‐atom nickel decorated carbon membranes with industry Electroactive bacteria—Molecular mechanisms and genetic tools. compatible current densities. Nature Communications, 11(1), 593. Applied Microbiology and Biotechnology, 98(20), 8481–8495. https://doi.org/10.1038/s41467-020-14402-0 Szczesny, J., Ruff, A., Oliveira, A. R., Pita, M., Pereira, I. A. C., Yang, Z., Li, D., Xing, L., Xiang, H., Xuan, J., Cheng, S., Yu, E. H., & Yang, A. De Lacey, A. L., & Schuhmann, W. (2020). Electroenzymatic CO2 (2021). Modeling and upscaling analysis of gas diffusion electrode‐ fixation using redox polymer/enzyme‐modified gas diffusion elec- based electrochemical carbon dioxide reduction systems. ACS trodes. ACS Energy Letters, 5(1), 321–327. https://doi.org/10.1021/ Sustainable Chemistry & Engineering, 9(1), 351–361. https://doi.org/ acsenergylett.9b02436 10.1021/acssuschemeng.0c07387 10970290, 2023, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/bit.28383 by Readcube (Labtiva Inc.), Wiley Online Library on [07/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License STÖCKL ET AL. | 1477 Yishai, O., Lindner, S. N., Gonzalez de la Cruz, J., Tenenboim, H., & chemicals. Biotechnology for Biofuels, 11(1), 260. https://doi.org/10. Bar‐Even, A. (2016). The formate bio‐economy. Current Opinion in 1186/s13068-018-1265-y Chemical Biology, 35, 1–9. https://doi.org/10.1016/j.cbpa.2016. Zhang, X., He, W., Ren, L., Stager, J., Evans, P. J., & Logan, B. E. (2015). 07.005 COD removal characteristics in air‐cathode microbial fuel cells. You, S., Zhao, Q., Zhang, J., Jiang, J., Wan, C., Du, M., & Zhao, S. (2007). A Bioresource Technology, 176, 23–31. graphite‐granule membrane‐less tubular air‐cathode microbial fuel Zhao, F., Harnisch, F., Schröder, U., Scholz, F., Bogdanoff, P., & Herrmann, I. cell for power generation under continuously operational conditions. (2006). Challenges and constraints of using oxygen cathodes in microbial Journal of Power Sources, 173(1), 172–177. fuel cells. Environmental Science & Technology, 40(17), 5193–5199. Yuan, M., Kummer, M. J., Milton, R. D., Quah, T., & Minteer, S. D. (2019). https://doi.org/10.1021/es060332p Efficient NADH regeneration by a redox polymer‐immobilized enzymatic system. ACS Catalysis, 9(6), 5486–5495. https://doi.org/ 10.1021/acscatal.9b00513 Zhang, C., Zhang, H., Pi, J., Zhang, L., & Kuhn, A. (2022). Bulk How to cite this article: Stöckl, M., Lange, T., Izadi, P., electrocatalytic NADH cofactor regeneration with bipolar Bolat, S., Teetz, N., Harnisch, F., & Holtmann, D. (2023). electrochemistry. Angewandte Chemie (International ed. in Application of gas diffusion electrodes in bioeconomy: English), 61(3), e202111804. https://doi.org/10.1002/anie.202 111804 An update. Biotechnology and Bioengineering, 120, Zhang, W., Song, M., Yang, Q., Dai, Z., Zhang, S., Xin, F., Dong, W., Ma, J., 1465–1477. https://doi.org/10.1002/bit.28383 & Jiang, M. (2018). Current advance in bioconversion of methanol to