Topics in Current Chemistry (2018) 376:43
1 3
along the protein surfaces between the malate dehydrogenase-citrate synthase active
sites and the citrate synthase-aconitase active sites [43]. These electrostatic surface
pathways are oppositely charged to the shared reaction intermediate between adjacent
enzymes and were proposed (and later experimentally confirmed [44]) as electrostatic
channels to minimize intermediate diffusion into the bulk solution. This mechanism,
termed electrostatic substrate channeling, has been the focus of growing interest as a
design tool for controlling intermediate flux in artificial catalytic cascades [45]. While
recent studies have suggested that electrostatic substrate channeling in enzymes occurs
via discrete interactions between charged intermediates and oppositely charged solvent
accessible amino acid residues [46–48], a precise understanding of this mechanism in
artificial cascades is still being developed. Furthermore, continuing research is needed
to define the role and limitations of substrate channeling as a design principle in artificial catalytic cascades.
7 Conclusion
In summary, electrochemical catalytic cascades can be used for complex fuel oxidation to yield high current and energy densities compared to individual components of the cascade. These cascades also benefit from substrate specificity
and mild reaction conditions. As artificial electrometabolic pathways become
more complex to facilitate multi-step oxidations, cascades become limited by
diffusional and kinetic properties (Fig. 7). These limitations can be overcome
by employing molecular architectures that enable precise spatial orientation of
sequential catalysts, and continuing research may incorporate substrate channeling as a means of restricting diffusion of intermediates beyond simple proximity effects.
Acknowledgements The authors would like to thank the Army Research Office MURI
award (W911NF-14-1-0263) for funding.
References
1. Sundaresan VB, Sarles SA, Leo DJ (2006) Stack of BioCells converting ATP to electrical power
and possible applications. MRS Proc. https ://doi.org/10.1557/proc-0950-d01-03
2. Qian H, Autzen Henriette E (2012) A little engine that could: ATP-powered electrical battery
and heater inside cells. Biophys J 103(7):1409–1410. https ://doi.org/10.1016/j.bpj.2012.08.047
3. Chen Y, Choi S, Thompson LT (2015) Low-temperature CO 2 hydrogenation to liquid products
via a heterogeneous cascade catalytic system. ACS Cat 5(3):1717–1725. https ://doi.org/10.1021/
cs501 656x
4. Macazo FC, Minteer SD (2017) Enzyme cascades in biofuel cells. Curr Opin Electrochem
5(1):114–120. https ://doi.org/10.1016/j.coele c.2017.07.010
5. Szczupak A, Aizik D, Moraïs S, Vazana Y, Barak Y, Bayer E, Alfonta L (2017) The electrosome:
a surface-displayed enzymatic cascade in a biofuel cell’s anode and a high-density surface-displayed biocathodic enzyme. Nanomaterials 7(7):153
6. Wu G, Gao Y, Zhao D, Ling P, Gao F (2017) Methanol/oxygen enzymatic biofuel cell using
laccase and NAD + -dependent dehydrogenase cascades as biocatalysts on carbon nanodots
Reprinted from the journal
162
1 3
along the protein surfaces between the malate dehydrogenase-citrate synthase active
sites and the citrate synthase-aconitase active sites [43]. These electrostatic surface
pathways are oppositely charged to the shared reaction intermediate between adjacent
enzymes and were proposed (and later experimentally confirmed [44]) as electrostatic
channels to minimize intermediate diffusion into the bulk solution. This mechanism,
termed electrostatic substrate channeling, has been the focus of growing interest as a
design tool for controlling intermediate flux in artificial catalytic cascades [45]. While
recent studies have suggested that electrostatic substrate channeling in enzymes occurs
via discrete interactions between charged intermediates and oppositely charged solvent
accessible amino acid residues [46–48], a precise understanding of this mechanism in
artificial cascades is still being developed. Furthermore, continuing research is needed
to define the role and limitations of substrate channeling as a design principle in artificial catalytic cascades.
7 Conclusion
In summary, electrochemical catalytic cascades can be used for complex fuel oxidation to yield high current and energy densities compared to individual components of the cascade. These cascades also benefit from substrate specificity
and mild reaction conditions. As artificial electrometabolic pathways become
more complex to facilitate multi-step oxidations, cascades become limited by
diffusional and kinetic properties (Fig. 7). These limitations can be overcome
by employing molecular architectures that enable precise spatial orientation of
sequential catalysts, and continuing research may incorporate substrate channeling as a means of restricting diffusion of intermediates beyond simple proximity effects.
Acknowledgements The authors would like to thank the Army Research Office MURI
award (W911NF-14-1-0263) for funding.
References
1. Sundaresan VB, Sarles SA, Leo DJ (2006) Stack of BioCells converting ATP to electrical power
and possible applications. MRS Proc. https ://doi.org/10.1557/proc-0950-d01-03
2. Qian H, Autzen Henriette E (2012) A little engine that could: ATP-powered electrical battery
and heater inside cells. Biophys J 103(7):1409–1410. https ://doi.org/10.1016/j.bpj.2012.08.047
3. Chen Y, Choi S, Thompson LT (2015) Low-temperature CO 2 hydrogenation to liquid products
via a heterogeneous cascade catalytic system. ACS Cat 5(3):1717–1725. https ://doi.org/10.1021/
cs501 656x
4. Macazo FC, Minteer SD (2017) Enzyme cascades in biofuel cells. Curr Opin Electrochem
5(1):114–120. https ://doi.org/10.1016/j.coele c.2017.07.010
5. Szczupak A, Aizik D, Moraïs S, Vazana Y, Barak Y, Bayer E, Alfonta L (2017) The electrosome:
a surface-displayed enzymatic cascade in a biofuel cell’s anode and a high-density surface-displayed biocathodic enzyme. Nanomaterials 7(7):153
6. Wu G, Gao Y, Zhao D, Ling P, Gao F (2017) Methanol/oxygen enzymatic biofuel cell using
laccase and NAD + -dependent dehydrogenase cascades as biocatalysts on carbon nanodots
Reprinted from the journal
162