Angewandte Chemie,
Journal Year:
2024,
Volume and Issue:
136(48)
Published: Aug. 29, 2024
Abstract
Alpha‐ketoglutarate‐dependent
dioxygenases
(αKGDs)
have
recently
emerged
as
useful
biocatalysts
for
C−H
oxidation
and
functionalization.
In
this
work,
we
characterized
a
new
αKGD
from
aculene
biosynthesis,
AneA,
which
displays
broad
promiscuity
toward
number
of
substrates
with
different
ring
systems.
Unexpectedly,
AneA
was
found
to
be
capable
both
desaturation
hydroxylation
require
an
amino
ester
motif
on
its
substrate
productive
catalysis.
Insights
gathered
the
functional
characterization
substrate‐activity
profiling
enabled
development
chemoenzymatic
strategy
several
complex
sesquiterpenoids.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(13)
Published: Jan. 27, 2024
Biocatalytic
oxidations
are
an
emerging
technology
for
selective
C-H
bond
activation.
While
promising
a
range
of
oxidations,
practical
use
enzymes
catalyzing
aerobic
hydroxylation
is
presently
limited
by
their
substrate
scope
and
stability
under
industrially
relevant
conditions.
Here,
we
report
the
engineering
application
non-heme
iron
α-ketoglutarate-dependent
dioxygenase
direct
stereo-
regio-selective
non-native
fluoroindanone
en
route
to
oncology
treatment
belzutifan,
replacing
five-step
chemical
synthesis
with
enantioselective
hydroxylation.
Mechanistic
studies
indicated
that
formation
desired
product
was
enzyme
overoxidation,
these
properties
subsequently
improved
directed
evolution,
yielding
biocatalyst
capable
>15,000
total
turnovers.
Highlighting
industrial
utility
this
biocatalyst,
high-yielding,
green,
efficient
oxidation
demonstrated
at
kilogram
scale
belzutifan.
Chemical Science,
Journal Year:
2024,
Volume and Issue:
15(10), P. 3466 - 3484
Published: Jan. 1, 2024
The
second
coordination
sphere,
Asp721,
participates
in
a
hydrogen
bond
with
an
iron-coordinated
water
molecule,
thus
compensating
for
the
missing
facial
triad
carboxylate
AspH
and
enabling
stereoselective
C–H
oxidation.
Organic & Biomolecular Chemistry,
Journal Year:
2024,
Volume and Issue:
22(18), P. 3559 - 3583
Published: Jan. 1, 2024
This
review
highlights
the
recent
advancements
in
enzymatic
modifications
of
steroid
scaffolds,
emphasizing
hydroxylation,
ketoreduction,
dehydrogenation,
cascade
reactions,
and
other
modifications.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(3), P. 724 - 727
Published: Jan. 16, 2024
l-Isovaline
biosynthesis
by
TqaLFM-ti
from
Tolypocladium
inflatum
was
demonstrated
in
vitro.
The
biochemical
analysis
of
the
α-ketoglutarate-dependent
oxygenase
TqaL-ti
revealed
that
it
produces
(2S,3S)-3-ethyl-3-methylaziridine-2-carboxylic
acid
l-isoleucine,
thus
exhibiting
a
stereoselectivity
different
those
reported
homologues.
Remarkably,
single
mutation
on
I295
completely
exchanged
its
to
produce
C-3
stereoisomer.
TqaFM-ti
generates
d-isovaline
(2S,3R)-aziridine-2-carboxylic
acid,
suggesting
stereochemistry
TqaL
product
defines
isovaline.
Chinese Journal of Chemistry,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 18, 2025
Comprehensive
Summary
We
have
developed
a
series
of
1‐methylpyridine‐2(1
H
)‐thione
(MPT)
analogues
to
be
used
as
organocatalysts.
The
MPT
catalysts
are
easily
prepared
and
bench‐stable.
In
our
previous
work,
we
found
that
the
ground‐state
catalyst
could
act
nucleophile
generate
primary
radicals
via
an
S
N
2
pathway.
However,
this
reaction
was
limited
benzyl
radicals.
Herein,
reported
new
catalytic
property
catalyst.
photoexcited
(
E
(MPT
·+
/MPT*)
=
–1.60
V
vs.
Ag/AgCl
in
MeCN)
reduce
NHPI
esters
through
single
electron
transfer
process.
Various
carbon
radicals,
including
radical,
well
primary,
secondary
tertiary
alkyl
generated
easily.
Notably,
amino
acids,
peptide,
pharmaceuticals,
other
biologically
active
molecules
modified
by
using
methodology
showing
potential
synthetic
utility
method.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 28, 2025
2-oxoglutarate-dependent
non-heme
iron
hydroxylases
offer
a
direct
route
to
functionalizing
C(
sp
3
)–H
bonds
across
diverse
range
of
substrates,
making
them
prime
candidates
for
chemoenzymatic
synthetic
strategies.
We
demonstrate
the
ability
L-lysine
dioxygenase
perform
sequential
oxidation
and
computationally
explore
structural
elements
that
promote
this
reactivity.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(35), P. 19189 - 19194
Published: Aug. 25, 2023
Verruculogens
are
rare
fumitremorgin
alkaloids
that
contain
a
highly
unusual
eight-membered
endoperoxide.
In
this
paper,
we
report
concise
chemoenzymatic
synthesis
of
13-oxoverruculogen
using
enzymatic
C-H
peroxidation
and
rhodium-catalyzed
C-C
bond
activation
reactions
to
install
the
endoperoxide
pentacyclic
core
natural
product,
respectively.
Our
strategy
involves
use
13-epi-fumitremorgin
B
as
substrate
analog
for
endoperoxidation
by
verruculogen
synthase,
FtmOx1.
The
resulting
13-epi-verruculogen,
is
first
unnatural
generated
FtmOx1
used
in
13-oxoverruculogen.
This
enables
10-step
product
from
commercially
available
starting
materials
illustrates
hybrid
approach
utilizing
biocatalytic
transition-metal-catalyzed
access
challenging
alkaloid
architectures.
Moreover,
work
demonstrates
native
enzyme
promiscuity
viable
products.
Organic Letters,
Journal Year:
2024,
Volume and Issue:
26(15), P. 3263 - 3266
Published: April 10, 2024
The
ability
of
α-amanitin
to
potently
inhibit
RNA
polymerase
II
(RNAP
II)
has
elicited
further
research
into
its
use
as
a
novel
payload
for
antibody-drug
conjugates.
Despite
this
promise,
the
de
novo
synthesis
is
still
major
challenge
it
possesses
an
unusual
bicyclic
octapeptide
structure
that
contains
several
oxidized
amino
acids,
most
notably
4,5-dihydroxy-l-isoleucine.
Here,
we
report
concise
chemoenzymatic
key
acid
residue,
which
features
two
regioselective
and
diastereoselective
enzymatic
C–H
oxidations
on
l-isoleucine.
