Angewandte Chemie,
Год журнала:
2023,
Номер
136(7)
Опубликована: Сен. 9, 2023
Abstract
Biocatalysis
has
become
a
major
driver
in
the
innovation
of
preparative
chemistry.
Enzyme
discovery,
engineering
and
computational
design
have
matured
to
reliable
strategies
development
biocatalytic
processes.
By
comparison,
substrate
received
much
less
attention.
In
this
Minireview,
we
highlight
idea
that
synthetic
reagents
may
be
an
equally
fruitful
complementary
approach
develop
novel
enzyme‐catalysed
group
transfer
This
Minireview
discusses
key
examples
from
literature
illustrate
how
substrates
can
devised
improve
efficiency,
scalability
sustainability,
as
well
scope
such
reactions.
We
also
provide
opinion
concept
might
further
developed
future,
aspiring
replicate
evolutionary
success
story
natural
reagents,
adenosine
triphosphate
(ATP)
S
‐adenosyl
methionine
(SAM).
Chemical Communications,
Год журнала:
2023,
Номер
59(36), С. 5463 - 5466
Опубликована: Янв. 1, 2023
Methyltransferases
provide
excellent
specificity
in
late-stage
alkylation
of
biomolecules.
Their
dependence
on
S-adenosyl-L-methionine
(SAM)
mandates
efficient
access
to
SAM
analogues
for
biocatalytic
applications.
We
directly
compared
halide
methyltransferase
(HMT)
and
methionine
adenosyltransferase
(MAT)
explored
their
utility
cascade
reactions
with
NovO
regioselective,
Friedel-Crafts
a
coumarin.
The
HMT
efficiently
provided
methylation,
while
the
MAT
also
supplied
high
levels
reactions.
Abstract
Isophorone
is
a
relatively
small
molecule
with
several
neighboring
reacting
sites,
making
it
susceptible
to
various
competing
reactions
aldehydes,
including
aldol,
Baylis‐Hillman
(BH),
aldol
condensation,
and
Michael
addition
reactions.
In
the
present
work,
we
have
designed
switchable
1,8‐diazabicyclo[5.4.0]undec‐7‐ene
(DBU)‐catalyzed
procedure,
where
reaction
of
isophorone
aldehydes
guided
chemoselectively
toward
either
BH,
or
condensation
reactions,
depending
on
use
water
and/or
heat.
This
controllable
divergency
likely
stems
from
ability
tune
dual
nucleophilicity/basicity
characters
DBU/H
2
O
medium.
other
words,
nucleophilicity
DBU
plays
crucial
role
in
directing
process
formation
BH
adducts
absence
water.
At
same
time,
pathway
dominates
when
present.
The
conditions
were
amenable
for
tandem
processes,
as
demonstrated
an
condensation/Diels‐Alder
sequence.
Enzyme
engineering
aims
to
improve
or
install
a
new
function
in
biocatalysts
for
applications
ranging
from
chemical
synthesis
biomedicine.
For
decades,
computational
techniques
have
been
developed
predict
the
effect
of
protein
changes
and
design
enzymes.
However,
these
may
optimized
deal
with
proteins
composed
standard
amino
acid
alphabet,
while
many
enzymes
relies
on
non-proteogenic
parts
like
cofactors,
nucleic
acids,
post-translational
modifications.
systems
containing
such
molecules
might
be
handled
modeled
improperly
by
tools,
thus
unsuitable,
require
additional
tweaking,
parameterization,
preparation.
In
this
review,
we
give
an
overview
common
recent
tools
workflows
available
enzyme
engineers.
We
highlight
various
pitfalls
that
come
including
compounds
computations
outline
potential
ways
address
issues.
Finally,
showcase
successful
examples
literature
computationally
engineered
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
62(51)
Опубликована: Ноя. 2, 2023
Enzyme-catalyzed
late-stage
functionalization
(LSF),
such
as
methylation
of
drug
molecules
and
lead
structures,
enables
direct
access
to
more
potent
active
pharmaceutical
ingredients
(API).
S-adenosyl-l-methionine-dependent
methyltransferases
(MTs)
can
play
a
key
role
in
the
development
new
APIs,
they
catalyze
chemo-
regioselective
O-,
N-,
S-
C-atoms,
being
superior
traditional
chemical
routes.
To
identify
suitable
MTs,
we
developed
continuous
fluorescence-based,
high-throughput
assay
for
SAM-dependent
methyltransferases,
which
facilitates
screening
using
E.
coli
cell
lysates.
This
involves
two
enzymatic
steps
conversion
S-adenosyl-l-homocysteine
into
H
Angewandte Chemie International Edition,
Год журнала:
2023,
Номер
63(7)
Опубликована: Сен. 9, 2023
Abstract
Biocatalysis
has
become
a
major
driver
in
the
innovation
of
preparative
chemistry.
Enzyme
discovery,
engineering
and
computational
design
have
matured
to
reliable
strategies
development
biocatalytic
processes.
By
comparison,
substrate
received
much
less
attention.
In
this
Minireview,
we
highlight
idea
that
synthetic
reagents
may
be
an
equally
fruitful
complementary
approach
develop
novel
enzyme‐catalysed
group
transfer
This
Minireview
discusses
key
examples
from
literature
illustrate
how
substrates
can
devised
improve
efficiency,
scalability
sustainability,
as
well
scope
such
reactions.
We
also
provide
opinion
concept
might
further
developed
future,
aspiring
replicate
evolutionary
success
story
natural
reagents,
adenosine
triphosphate
(ATP)
S
‐adenosyl
methionine
(SAM).
Organic & Biomolecular Chemistry,
Год журнала:
2023,
Номер
21(42), С. 8488 - 8493
Опубликована: Янв. 1, 2023
The
paper
details
an
electrochemical
method
that
couples
olefins
with
benzotriazoles
to
form
C(sp2)-N
bonds,
enabling
the
synthesis
of
N-vinyl
in
moderate
good
yields.
nBu4NI
functions
as
both
electrolyte
and
iodine
mediator,
does
not
require
oxidants
or
metals.
It
is
a
highly
atom-economical
clean
reaction,
hydrogen
sole
byproduct.
The
ability
to
a
site-selectively
modify
equivalent
functional
groups
in
molecule
has
the
potential
streamline
syntheses
and
increase
product
yields
by
lowering
step
counts.
Enzymes
catalyze
site-selective
transformations
throughout
primary
secondary
metabolism,
but
leveraging
this
capability
for
non-native
substrates
reactions
requires
detailed
understanding
of
limitations
enzyme
catalysis
how
these
bounds
can
be
extended
protein
engineering.
In
review,
we
discuss
representative
examples
involving
group
manipulation
C-H
bond
functionalization.
We
include
illustrative
native
catalysis,
our
focus
is
on
cases
often
using
engineered
enzymes.
then
use
enzymes
chemoenzymatic
target-oriented
synthesis
conclude
with
survey
tools
techniques
that
could
expand
scope
catalysis.
