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Topics in Current Chemistry (2018) 376:43
3 Hybrid Cascades for Electrometabolic Glycerol Oxidation Pathways
Glycerol is a promising biofuel due to its low cost, abundance (it is a biproduct of
industrial biodiesel production) and its high energy density [23]. This is highlighted
by the fact that concentrated glycerol solutions boast theoretical energy densities
(6260 W h L
−1
) that are comparable to than gasoline [24]. However, designing electrometabolic pathways from glycerol that mimic natural metabolism is complicated
by the number of enzymes required for its activation to oxidation (as highlighted
by the complex pathways described above). Recent efforts to electrochemically oxidize glycerol to CO 2 have shifted towards a simpler artificial pathway by employing catalysts with lower substrate specificity. Arechederra et al. demonstrated that
three promiscuous enzymes [PQQ-dependent alcohol and aldehyde dehydrogenase
and oxalate oxidase (OxO)] can be used to catalyze the complete bioelectrooxidation
of glycerol to CO 2 [25]. The combination of alcohol and aldehyde dehydrogenases
was able to oxidize alcohol and aldehyde intermediates (five steps) along the electrometabolic glycerol pathway, eventually converting glycerol into mesoxalic acid
[26]. Then, oxalate oxidase was employed to cleave CO 2 from both mesoxalate and
oxalate to complete the cascade, while collecting 12 electrons per glycerol molecule
[25]. The primary drawback to this approach comes from the decreasing relative
activity as the catalytic cascade progresses. As such, the rate of electroenzymatic
glycerol oxidation (step 1) is much slower than the rate of tartronic acid oxidation
(step 5), which stems from the fact that, despite being a promiscuous enzyme, alcohol dehydrogenase maintains an activity bias for primary alcohols. To simplify the
system further and enable a more uniform reactivity, a novel strategy was developed
utilizing hybrid catalytic motifs.
Enzymes have evolved to exhibit exceptional catalytic activities towards a
relatively limited range of substrates, while small molecular catalysts have been
designed to comparatively moderate catalytic activity towards a much broader
substrate scope. Given the demands of complex electrooxidative cascades, it was
postulated that hybrid catalytic combinations could combine the benefits of each
catalytic motif. Hickey et al. employed a homogeneous small molecular catalyst,
2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), known to electrochemically
oxidize alcohols to aldehydes and subsequently to carboxylic acids under mild
aqueous conditions to replace alcohol and aldehyde dehydrogenases from the electrometabolic glycerol pathway described above [27]. One particular amine-functionalized derivative, TEMPO-NH 2 , was demonstrated to catalyze the first five
steps of the electrochemical glycerol oxidation pathway (as well as step 7, glyoxalate to oxalate), thereby replacing the catalytic role of both alcohol and aldehyde
dehydrogenase. Most importantly, TEMPO-NH 2 was found to exhibit exceptional
catalytic activity in the oxidation of tartrate, which had been the limiting step for
complete glycerol oxidation. The rate of electron transfer is substantially slower
for OxO than TEMPO-NH 2 . Consequently, most electrons from the OxO-catalyzed oxidative cleavage of mesoxalate and oxalate were likely leached to O 2 (the
Reprinted from the journal
155
Topics in Current Chemistry (2018) 376:43
3 Hybrid Cascades for Electrometabolic Glycerol Oxidation Pathways
Glycerol is a promising biofuel due to its low cost, abundance (it is a biproduct of
industrial biodiesel production) and its high energy density [23]. This is highlighted
by the fact that concentrated glycerol solutions boast theoretical energy densities
(6260 W h L
−1
) that are comparable to than gasoline [24]. However, designing electrometabolic pathways from glycerol that mimic natural metabolism is complicated
by the number of enzymes required for its activation to oxidation (as highlighted
by the complex pathways described above). Recent efforts to electrochemically oxidize glycerol to CO 2 have shifted towards a simpler artificial pathway by employing catalysts with lower substrate specificity. Arechederra et al. demonstrated that
three promiscuous enzymes [PQQ-dependent alcohol and aldehyde dehydrogenase
and oxalate oxidase (OxO)] can be used to catalyze the complete bioelectrooxidation
of glycerol to CO 2 [25]. The combination of alcohol and aldehyde dehydrogenases
was able to oxidize alcohol and aldehyde intermediates (five steps) along the electrometabolic glycerol pathway, eventually converting glycerol into mesoxalic acid
[26]. Then, oxalate oxidase was employed to cleave CO 2 from both mesoxalate and
oxalate to complete the cascade, while collecting 12 electrons per glycerol molecule
[25]. The primary drawback to this approach comes from the decreasing relative
activity as the catalytic cascade progresses. As such, the rate of electroenzymatic
glycerol oxidation (step 1) is much slower than the rate of tartronic acid oxidation
(step 5), which stems from the fact that, despite being a promiscuous enzyme, alcohol dehydrogenase maintains an activity bias for primary alcohols. To simplify the
system further and enable a more uniform reactivity, a novel strategy was developed
utilizing hybrid catalytic motifs.
Enzymes have evolved to exhibit exceptional catalytic activities towards a
relatively limited range of substrates, while small molecular catalysts have been
designed to comparatively moderate catalytic activity towards a much broader
substrate scope. Given the demands of complex electrooxidative cascades, it was
postulated that hybrid catalytic combinations could combine the benefits of each
catalytic motif. Hickey et al. employed a homogeneous small molecular catalyst,
2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), known to electrochemically
oxidize alcohols to aldehydes and subsequently to carboxylic acids under mild
aqueous conditions to replace alcohol and aldehyde dehydrogenases from the electrometabolic glycerol pathway described above [27]. One particular amine-functionalized derivative, TEMPO-NH 2 , was demonstrated to catalyze the first five
steps of the electrochemical glycerol oxidation pathway (as well as step 7, glyoxalate to oxalate), thereby replacing the catalytic role of both alcohol and aldehyde
dehydrogenase. Most importantly, TEMPO-NH 2 was found to exhibit exceptional
catalytic activity in the oxidation of tartrate, which had been the limiting step for
complete glycerol oxidation. The rate of electron transfer is substantially slower
for OxO than TEMPO-NH 2 . Consequently, most electrons from the OxO-catalyzed oxidative cleavage of mesoxalate and oxalate were likely leached to O 2 (the
Reprinted from the journal
155