Chemoenzymatic cascade for stilbene production from cinnamic acid catalyzed by ferulic acid decarboxylase and an artificial metathease

Article abstract of DOI:10.1039/c9cy01412h

We report the preparation of symmetrical stilbene derivatives in a two-step one-pot cascade reaction based on enzymatic decarboxylation of cinnamic acid followed by olefin cross metathesis. Embedment of the metathesis catalyst in a protein scaffold enabled the cascade reaction to symmetric stilbenes and furthermore very efficient removal of metal impurities (<1 ppm in product fraction).

Full text of DOI:10.1039/c9cy01412h

Catalysis
Science &
Technology
View Article Online
View Journal | View Issue
COMMUNICATION
Chemoenzymatic cascade for stilbene production
from cinnamic acid catalyzed by ferulic acid
decarboxylase and an artificial metathease†
Cite this: Catal. Sci. Technol., 2019,
9, 5572
Received 18th July 2019,
Accepted 12th September 2019
a
M. A. Stephanie Mertens, ‡a Daniel F. Sauer, ‡a Ulrich Markel,
a
ac
b and Ulrich Schwaneberg
*
*
Johannes Schiffels,
Jun Okuda
DOI: 10.1039/c9cy01412h
rsc.li/catalysis
We report the preparation of symmetrical stilbene derivatives in a
two-step one-pot cascade reaction based on enzymatic
decarboxylation of cinnamic acid followed by olefin cross
metathesis. Embedment of the metathesis catalyst in a protein
scaffold enabled the cascade reaction to symmetric stilbenes and
furthermore very efficient removal of metal impurities (<1 ppm in
product fraction).
derivatives, this reaction yields styrene derivatives that could
be further converted to stilbene derivatives via olefin cross
metathesis.14 Owing to the electron poor double bond in
cinnamic acid derivatives, this conversion has hitherto not
been efficiently achieved using common olefin metathesis
catalysts. Stilbene derivatives are building blocks for many
biologically active compounds (i.e., pharmaceuticals). For
instance, symmetrical stilbene derivatives were shown to
effectively induce apoptosis in human cancer cell lines or act
as modulators of hormone receptors.15,16
Kourist and co-workers developed a one-pot cascade reaction
to convert hydroxycinnamic acids to 4,4′-dihydroxystilbene
derivatives by employing a chemoenzymatic approach involving
decarboxylation and olefin metathesis.12 Compatibility between
the decarboxylase (BsPAD – Bacillus subtilis phenolic acid
decarboxylase) and the olefin metathesis catalyst was ensured
by compartmentalization (i.e., encapsulation) of the enzyme
Chemoenzymatic
cascade
reactions
are
intriguing
developments in synthetic organic chemistry. They combine
the broad reaction scope of chemical catalysis with the
unparalleled regio- and enantioselectivity of biocatalysts.1–3 In
such cascades, reactive intermediates are promptly converted
to a desired product, suppressing side product formation or
enzyme inhibition. Moreover, as the isolation of
intermediates is not necessary, the process as a whole
becomes more (cost-)efficient.4,5 The types of catalysts
employed in such cascades are manifold. Yet, challenges
concerning compatibility are often initially faced.6,7 Metal
catalysts can be poisoned by protein- or whole-cell-borne
functional groups, commonly resulting in mutual deactivation
of the metal catalyst and the enzyme. Therefore, reaction
conditions that are suitable for both catalysts need to be
into PVA/PEG beads (PVA
= polyIJvinyl alcohol); PEG =
poly(ethylene glycol)).12 Still, the best results were achieved
when the solvent was exchanged by MTBE, followed by addition
of anhydrous MgSO4 to obtain a dry reaction medium for the
olefin metathesis step. In a subsequent work, the Kourist group
presented a similar reaction sequence involving decarboxylation
of fatty acids by cytochrome P450 OleT from Jeotgalicoccus sp.
ATCC 8456 (OleTJE) followed by olefin cross metathesis.8
Hartwig, Zhao and co-workers demonstrated the combination
of a Grubbs–Hoveyda type olefin metathesis catalyst and a P450
monooxygenase for epoxidation.9,10
established. An example for
a bioorthogonal chemical
transformation that could be coupled to an enzymatic
reaction8–12 is offered by olefin metathesis, in which CC
double bonds are rearranged.13
Aqueous decarboxylation reactions are catalyzed by
enzymes coined decarboxylases. Applied to cinnamic acid
Ring-closing metathesis (RCM) in combination with
enzymatic catalysis was shown by Gröger et al.11 In a
two-step one-pot reaction, diethyl malonates were
converted via RCM to the corresponding cyclic alkenes
followed by enzymatic saponification of the ester.11 All
studies mentioned above showed that it is in principle
possible to combine olefin metathesis with biocatalysis.
However, efficient conversion by both catalysts always
required their spatial separation to avoid mutual
inactivation.
a Institute of Biotechnology, RWTH Aachen University, Worringerweg 3, 52074
Aachen, Germany. E-mail: u.schwaneberg@biotec.rwth-aachen.de
b Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, 52074
Aachen, Germany. E-mail: jun.okuda@ac.rwth-aachen.de
c DWI-Leibniz Institute for Interactive Materials, Forckenbeckstraße 50, 52056
Aachen, Germany
† Electronic supplementary information (ESI) available. See DOI: 10.1039/
c9cy01412h
‡ These authors contributed equally to this work.
5572 | Catal. Sci. Technol., 2019, 9, 5572–5576
This journal is © The Royal Society of Chemistry 2019

View Article Online
Catalysis Science & Technology
Communication
In all these examples, relatively high metal catalyst
loadings (∼5 mol%) were required, especially if the
metathesis step succeeded the enzymatic step. It is assumed
that this is based on the inactivation of the metal catalyst by
unspecific coordination to proteins. High catalyst loadings
entail the necessity for metal removal in a post-reaction step.
The latter is of paramount importance if the desired product
is used for pharmaceutical applications.17
Fig. 1 Biohybrid catalyst FhuA-GH 3 consisting of the transmembrane
protein FhuA and the immobilized Grubbs–Hoveyda type catalyst
(right).
Biohybrid catalysts (BHCs), also dubbed artificial
metalloproteins, are attractive tools to achieve the spatial
separation of chemoenzymatic reaction steps and to facilitate
metal removal post-reaction. In BHCs, the transition metal
catalyst is embedded in a protein scaffold that lacks an
intrinsic catalytic activity.18–25 In this way, organometallic
catalysts can be immersed in an aqueous reaction medium
and the reaction scope of biocatalysis can be enhanced by
new-to-nature reactions. So far, the one-pot combination of a
BHC and an enzyme was demonstrated only for the purpose
of regenerating cofactors such as NAD(P)H either by the
enzyme or the BHC.26–28 The potential of BHC/enzyme
combinations in sequential cascade reactions beyond the
regeneration of cofactors has not been explored.
Herein, we report a one-pot cascade reaction to produce
stilbene derivatives 4a–b from cinnamic acids in aqueous
solution by combining an enzyme and a BHC (Scheme 1). In
our approach, the decarboxylation of cinnamic acids 1a–b to
styrene derivatives 5a–b was catalyzed by ferulic acid
decarboxylase (FDC1) from Saccharomyces cerevisiae
(S. cerevisiae). The styrene intermediates were further
converted by an olefin metathesis BHC that is composed of
an engineered variant of the outer membrane protein Ferric
activity. In vivo synthesis of the cofactor is accomplished by
phenolic acid decarboxylase (PAD1).33 In this study, the genes
encoding FDC1 and tPAD1 were codon-optimized and co-
expressed in E. coli to debottleneck the assembly of the
functional recombinant enzyme. tPAD1 is a truncated version
of PAD1 lacking a mitochondrial targeting sequence, which is
redundant for expression in E. coli.34 FDC1 converts
cinnamic acids to styrenes at a pH range of 6–834–36and at
temperatures up to 45 °C.35 This reaction requires no
additional cofactors such as NAD(P)H, which obviates the
need for cofactor regeneration systems. FDC1 converts a wide
range of substrates carrying different substitutions at the
substrate's aromatic moiety.33 Taken together, these features
make FDC1 an intriguing candidate for implementation in
cascade reactions together with bioorthogonal olefin
metathesis BHCs.
For olefin metathesis, we employed
a
previously
introduced BHC consisting of an engineered variant of FhuA
and a Grubbs–Hoveyda type catalyst.29–31 FhuA is an outer-
membrane β-barrel protein stable at temperatures up to 64
°C.37 Moreover, the protein retains its structural integrity in
the presence of organic co-solvents like THF (up to 40 (v/v)%).38
The use of organic co-solvents enables the use of substrates
exhibiting low water solubility. To solubilize the membrane
protein, sodium dodecyl sulfate (SDS) was used as previously
described.29,30 First, biocatalyst FDC1 (2) was probed in the
decarboxylation of substrates 1a and 1b (Table 1). At low pH
values (pH < 6) that are beneficial for the subsequent olefin
metathesis step, the substrates 1a and 1b are moderately
soluble in aqueous buffer solution. Therefore, different co-
solvents were tested for substrate solubilization. DMSO
inhibited the Grubbs–Hoveyda catalyst and was therefore
deemed unsuitable for the cascade.
hydroxamate uptake protein component:
A (FhuA) of
Escherichia coli (E. coli), equipped with a covalently anchored
Grubbs–Hoveyda type catalyst (Fig. 1).29–31 The resulting BHC
is stable in aqueous solution for more than
a week
(confirmed by titration with ThioGlo) without detectable
protein precipitation or any indication for a detachment of
the metal catalyst.
Decarboxylation is an important and ubiquitous metabolic
reaction in both prokaryotes and eukaryotes. Several
decarboxylases have been characterized.32 S. cerevisiae
harbors a ferulic acid decarboxylase (FDC1) that requires a
prenylated flavin mononucleotide (FMN) cofactor for catalytic
In the presence of 7.5 (v/v)% THF at 30 °C, 1a was
converted to 5a at 86% yield (Table 1, entry 1). When the
temperature was elevated to 35 °C, the yield dropped to 73%
(Table 1, entry 2). A similar behavior was observed for
substrate 1b, resulting in yields of 99% and 58% at 30 °C and
35 °C, respectively (Table 1, entries 3 and 4). Decreasing the
THF concentration to
5 (v/v)% afforded an increased
conversion of 1a to 5a with 91% and 87% at 30 °C and 35 °C,
respectively (Table 1, entry 5 and 6). Substrate 1b was
quantitatively converted to 5b at 30 °C or 35 °C (Table 1, entry
7 and 8), suggesting a preferred acceptance of this substrate
by FDC1 under the investigated conditions. It is surmised that
Scheme 1 Chemoenzymatic cascade reaction starting from cinnamic
acid derivatives 1 that are decarboxylated by biocatalyst 2 to yield
styrene derivatives which are transformed into stilbene derivatives 4 by
the biohybrid catalyst FhuA-GH 3.
This journal is © The Royal Society of Chemistry 2019
Catal. Sci. Technol., 2019, 9, 5572–5576 | 5573

View Article Online
Communication
Catalysis Science & Technology
Table 1 Decarboxylation of cinnamic acid derivatives 1 by cell-free extracts containing the recombinant biocatalyst 2 (FDC1)
Entry
Substrate
THF [(v/v)%]
T [°C]
[%] 1
[%] 5
1
2
3
4
5
6
7
8
1a
1a
1b
1b
1a
1a
1b
1b
7.5
7.5
7.5
7.5
5
5
5
5
30
35
30
35
30
35
30
35
13
26
<1
41
8
12
<1
<1
86
73
>99
58
91
87
>99
>99
Conversion were determined by GC-FID. The conversions of 12 mM 1a–b were performed with 15 μM FDC1 (cell-free extract) in sodium
phosphate buffer (100 mM, 137 mM NaCl, pH 6.0). The reactions were run for 1 h. Δconv. = 2%.
the chloro-substituent at the styrene mimics the natural
substrate of the FDC1.36 In summary, 5 (v/v)% THF was
determined as the most suitable co-solvent concentration
tolerable for FDC1 in the cascade reaction (Table 1, entries 5–
8). Next, we aimed to determine conditions under which both
catalysts would be active. Increasing the temperature slightly
lowered the conversion efficiency of FDC1 (Table 1, entries 2,
4, 6 and 8). In turn, slightly acidic conditions (pH 6) that are
necessary for the subsequent olefin metathesis step still
afforded reasonable conversions despite the enzyme's pH-
optimum being at pH 7–8.39
With suitable conditions for the first conversion step in
hand, the two catalysts to produce stilbene derivatives from
cinnamic acid derivatives were combined. As expected, in the
absence of the catalysts, no conversion of substrates 1a or 1b
was detected (Table 2, entry 1). Likewise, the corresponding
stilbene derivative was not formed when only the biocatalyst
FDC1 was present.
BHC 3 and AquaMet40 6 (a commercially available and
water-soluble Grubbs–Hoveyda type catalyst; for chemical
structure see ESI† Fig. S4) were probed in the conversion of
the cinnamic acid derivatives to obtain stilbene derivatives.
Expectedly, reactions with both catalysts yielded only trace
amounts (<1%) of the respective stilbene derivatives as
determined by GC-MS (Table 2, entries 2 and 3). Upon
combining biocatalyst 2 with either BHC 3 or AquaMet 6
directly at reaction start (‘concurrent mode’), less than 5% of
products 5a or 5b were formed (Table 2, entries 4 and 5). The
low conversion efficiency indicates a deactivation of the
decarboxylase 2 by the catalyst AquaMet 6 (Table 2, entry 4),
or by the SDS detergent used for solubilization of BHC 3
(Table 2, entry 5).41 Therefore, we employed an alternative
approach, in which catalyst 3 or 6 were added subsequently
after completion of the decarboxylation reaction (‘sequential
mode’). Again, the combination of biocatalyst 2 and AquaMet
6 yielded only traces of the corresponding stilbene derivatives
Table 2 Two-step one-pot reaction for stilbene production
Entry
Substrate
Catalyst
1 [%]
5 [%]
4 [%]
1
2
3
1a/b
1a
1a
1a
1a
1a
1b
1a
—
3
6
2, 6
2, 3
2, 6
2, 6
2, 3
2, 3
>99
>98
>98
>95
>95
<1
<1
<1
<1
—
—
—
<5
<5
>98
>98
25
—
<1
<1
—
4a
5a
6b
7b
8b
9b
—
<1
<1
74
64
1b
35
Conversions were determined by GC-MS. The conversions of 12 mM 1a–b were performed with 15 μM FDC1 (cell-free extract) in sodium phosphate
buffer (100 mM, 137 mM NaCl, 5 (v/v)% THF, pH 6.0) at 35 °C. Addition of 3 mol% biohybrid catalyst 3 or AquaMet 6 in sodium phosphate buffer
a
(100 mM, pH 6.0, final 0.04 (w/v)% SDS, 50 mM NaCl and 2 (v/v)% THF) initiated the subsequent olefin metathesis step. Directly (concurrent
mode, 6 h reaction time). b After 1 h (sequential mode) and further conversion for additional 4 h at 35 °C. Δ1/5/4 = 3%.
5574 | Catal. Sci. Technol., 2019, 9, 5572–5576
This journal is © The Royal Society of Chemistry 2019

View Article Online
Catalysis Science & Technology
Communication
from substrates 1a/b via 5a/b (Table 2, entries 6 and 7). This
finding is in agreement with previous reports showing that
‘unprotected’ metal catalysts are prone to inactivation by cell
lysate contents like glutathione.7 Finally, when biocatalyst 2
and BHC 3 were combined in a sequential cascade reaction,
74% of the product 4a and 64% of 4b were detected (Table 2,
entry 8 and 9). This suggests that by embedding the metal
contamination in the product fraction was remarkably low
after performing one simple extraction step with
dichloromethane. This shows that by immobilizing the
catalyst in a protein cavity, we can not only combine aqueous
biocatalysis with organic synthesis, but also facilitate sample
workup and product isolation.
catalyst into the protein scaffold provided by FhuA, the metal Conflicts of interest
site is shielded from inhibition.
There are no conflicts to declare.
Furthermore, unspecific coordination of the protein-free
metal catalyst to proteins present in the reaction mixture
appears to be circumvented by immobilizing (and
Acknowledgements
embedding) the GH-type catalyst in the protein scaffold.
We gratefully acknowledge financial support by the German
Compared to previously reported cascade reactions
combining decarboxylation and olefin metathesis, the
cascade reaction reported here does not require the use of
PVA/PEG beads in MTBE.12 Through immobilization of the
metal catalyst into a protein scaffold, the cascade reaction is
enabled in aqueous solution.
Research Foundation (DFG) through the International
Research Training Group “Selectivity in Chemo- and
Biocatalysis” as well as the BMBF (FKZ: 031B0297). We thank
Umicore, Frankfurt (Dr. A. Doppiu) for the generous gift of
ruthenium precursor.
An important challenge surrounding Ru-based catalysts
(e.g., for olefin metathesis) is the removal of metal
contaminations upon product workup. This is particularly
important in the case of pharmaceutical compounds, for
which the transition metal content should be typically below
10 ppm.17 A possible solution to this challenge could be
offered by adding a Ru scavenger after the reaction and
performing column chromatography, which has been
successfully applied, previously.42 It is already known from
the work by Hoveyda et al. that metal leaching from Grubbs–
Hoveyda type catalysts is relatively low.43 In the present work,
we hypothesized that BHC 3 (bearing the metal catalyst by
covalent attachment) could be readily separated from the
product fraction by performing a simple extraction step.
Indeed, ICP analysis of the product fractions gave Ru
contents as low as 1 ppm, whereas in the product fraction of
the same reaction setup with the water-soluble catalyst
AquaMet 6, 36 ppm Ru were detected (see ESI† for details).
This highlights the feasibility of BHCs for facile catalyst
removal.
Notes and references
1 F. Rudroff, M. D. Mihovilovic, H. Gröger, R. Snajdrova, H.
Iding and U. T. Bornscheuer, Nat. Catal., 2018, 1, 12–22.
2 E. García-Junceda, I. Lavandera, D. Rother and J. H.
Schrittwieser, J. Mol. Catal. B: Enzym., 2015, 114, 1–6.
3 F. Dumeignil, M. Guehl, A. Gimbernat, M. Capron, N. L.
Ferreira, R. Froidevaux, J.-S. Girardon, R. Wojcieszak, P.
Dhulster and D. Delcroix, Catal. Sci. Technol., 2018, 8,
5708–5734.
4 Y. Hayashi, Chem. Sci., 2016, 7, 866–880.
5 J. M. Sperl and V. Sieber, ACS Catal., 2018, 8, 2385–2396.
6 S. Schmidt, K. Castiglione and R. Kourist, Chem. – Eur. J.,
2018, 24, 1755–1768.
7 Y. M. Wilson, M. Dürrenberger, E. S. Nogueira and T. R.
Ward, J. Am. Chem. Soc., 2014, 136, 8928–8932.
8 S. Bojarra, D. Reichert, M. Grote, Á. G. Baraibar, A. Dennig,
B. Nidetzky, C. Mügge and R. Kourist, ChemCatChem,
2018, 10, 1192–1201.
9 C. A. Denard, M. J. Bartlett, Y. Wang, L. Lu, J. F. Hartwig and
H. Zhao, ACS Catal., 2015, 5, 3817–3822.
10 C. A. Denard, H. Huang, M. J. Bartlett, L. Lu, Y. Tan, H.
Zhao and J. F. Hartwig, Angew. Chem., Int. Ed., 2014, 53,
465–469.
11 K. Tenbrink, M. Seßler, J. Schatz and H. Gröger, Adv. Synth.
Catal., 2011, 353, 2363–2367.
12 Á. Gómez Baraibar, D. Reichert, C. Mügge, S. Seger, H.
Gröger and R. Kourist, Angew. Chem., Int. Ed., 2016, 55,
14823–14827.
13 R. H. Grubbs, A. G. Wenzel, D. J. O'Leary and E. Khosravi,
Handbook of Metathesis, Wiley-VCH, Weinheim, 2015.
14 I. Barbara, A. L. Flourat and F. Allais, Eur. Polym. J.,
2015, 62, 236–243.
15 S. Fulda, Drug Discovery Today, 2010, 15, 757–765.
16 I. Koszela-Piotrowska, K. Choma, P. Bednarczyk, K. Dołowy,
A. Szewczyk, W. S. Kunz, L. Malekova, V. Kominkova and K.
Ondrias, Cell. Mol. Biol. Lett., 2007, 12, 493–508.
In conclusion, the combination of biocatalysis employing
cell-free extracts – a cheap and easily obtainable source of the
recombinant biocatalyst – as well as organometallic catalysts
embedded in proteins provides a versatile tool to produce
valuable compounds from renewable resources. Stilbene
derivatives were produced in a one-pot cascade reaction
starting from cinnamic acid derivatives. Biocatalyst FDC1 (2)
in combination with
a BHC for olefin metathesis (3)
performed the stepwise conversion of cinnamic acid
derivatives (1) to stilbenes (4) under mild reaction conditions
in aqueous solution. Intermediate workup steps to isolate the
styrene derivatives were not necessary, since both reactions
proceeded in the same aqueous medium. Moreover, we have
shown that by using the BHC instead of ‘free’ metal catalysts
for olefin metathesis, changing the reaction conditions can
be circumvented, since the olefin metathesis step can be
performed in aqueous solution. Furthermore, metal
This journal is © The Royal Society of Chemistry 2019
Catal. Sci. Technol., 2019, 9, 5572–5576 | 5575

View Article Online
Communication
Catalysis Science & Technology
17 E. M. Agency, Specification limits for residues of metal
catalysts CHMP/SWP/4446/2000, 2008.
18 J. C. Lewis, ACS Catal., 2013, 3, 2954–2975.
19 F. Schwizer, Y. Okamoto, T. Heinisch, Y. Gu, M. M.
Pellizzoni, V. Lebrun, R. Reuter, V. Köhler, J. C. Lewis and
T. R. Ward, Chem. Rev., 2017, 118, 142–231.
20 J. Bos and G. Roelfes, Curr. Opin. Chem. Biol., 2014, 19,
135–143.
21 D. F. Sauer, S. Gotzen and J. Okuda, Org. Biomol. Chem.,
2016, 14, 9174–9183.
22 D. F. Sauer, J. Schiffels, T. Hayashi, U. Schwaneberg and J.
Okuda, Beilstein J. Org. Chem., 2018, 14, 2861–2871.
23 J. Steinreiber and T. R. Ward, Coord. Chem. Rev., 2008, 252,
751–766.
24 M. Hoarau, C. Hureau, E. Gras and P. Faller, Coord. Chem.
Rev., 2016, 308(Part 2), 445–459.
31 D. F. Sauer, Y. Qu, M. A. S. Mertens, J. Schiffels, T. Polen, U.
Schwaneberg and J. Okuda, Catal. Sci. Technol., 2019, 9,
942–946.
32 R. Kourist, J.-K. Guterl, K. Miyamoto and V. Sieber,
ChemCatChem, 2014, 6, 689–701.
33 K. A. Payne, M. D. White, K. Fisher, B. Khara, S. S. Bailey, D.
Parker, N. J. Rattray, D. K. Trivedi, R. Goodacre, R.
Beveridge, P. Barran, S. E. Rigby, N. S. Scrutton, S. Hay and
D. Leys, Nature, 2015, 522, 497–501.
34 F. Lin, K. L. Ferguson, D. R. Boyer, X. N. Lin and E. N. G.
Marsh, ACS Chem. Biol., 2015, 10, 1137–1144.
35 G. A. Aleku, C. Prause, R. T. Bradshaw-Allen, K. Plasch, S. M.
Glueck, S. S. Bailey, K. A. P. Payne, D. A. Parker, K. Faber
and D. Leys, ChemCatChem, 2018, 10, 4043–4052.
36 N. Mukai, K. Masaki, T. Fujii, M. Kawamukai and H. Iefuji,
J. Biosci. Bioeng., 2010, 109, 564–569.
25 U. Markel, D. F. Sauer, J. Schiffels, J. Okuda and U.
Schwaneberg, Angew. Chem., Int. Ed., 2019, 58, 4454–4464.
26 Y. Okamoto, V. Köhler and T. R. Ward, J. Am. Chem. Soc.,
2016, 138, 5781–5784.
27 Y. Okamoto, V. Köhler, C. E. Paul, F. Hollmann and T. R.
Ward, ACS Catal., 2016, 6, 3553–3557.
28 V. Köhler, Y. M. Wilson, M. Dürrenberger, D. Ghislieri, E.
Churakova, T. Quinto, L. Knörr, D. Häussinger, F.
Hollmann, N. J. Turner and T. R. Ward, Nat. Chem., 2013(5),
93–99.
37 M. Bonhivers, M. Desmadril, G. S. Moeck, P. Boulanger, A.
Colomer-Pallas and L. Letellier, Biochemistry, 2001, 40,
2606–2613.
38 S.-J. Tenne and U. Schwaneberg, Int. J. Mol. Sci., 2012, 13,
2459–2471.
39 E. Z. A. Nagy, C. L. Nagy, A. Filip, K. Nagy, E. Gál, R. Tőtős,
L. Poppe, C. Paizs and L. C. Bencze, Sci. Rep., 2019, 9, 647.
40 K. Skowerski, G. Szczepaniak, C. Wierzbicka, L. Gulajski, M.
Bieniek and K. Grela, Catal. Sci. Technol., 2012, 2,
2424–2427.
29 F. Philippart, M. Arlt, S. Gotzen, S.-J. Tenne, M. Bocola,
H.-H. Chen, L. Zhu, U. Schwaneberg and J. Okuda, Chem. –
Eur. J., 2013, 19, 13865–13871.
30 D. F. Sauer, M. Bocola, C. Broglia, M. Arlt, L.-L. Zhu, M.
Brocker, U. Schwaneberg and J. Okuda, Chem. – Asian J.,
2015, 10, 177–182.
41 D. Clark, N. Pazdernik and M. McGehee, Molecular Biology,
Academic Press (Elsevier), Waltham, MA, 2019.
42 G. Szczepaniak, K. Urbaniak, C. Wierzbicka, K. Kosiński, K.
Skowerski and K. Grela, ChemSusChem, 2015, 8, 4139–4148.
43 S. B. Garber, J. S. Kingsbury, B. L. Gray and A. H. Hoveyda,
J. Am. Chem. Soc., 2000, 122, 8168–8179.
5576 | Catal. Sci. Technol., 2019, 9, 5572–5576
This journal is © The Royal Society of Chemistry 2019