Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Aug. 9, 2023
Although
enzyme
catalysis
is
typified
by
high
specificity,
enzymes
can
catalyze
various
substrates
(substrate
promiscuity)
and/or
different
reaction
types
(catalytic
using
a
single
active
site.
This
interesting
phenomenon
widely
distributed
in
catalysis,
with
both
fundamental
and
applied
importance.
To
date,
the
mechanistic
understanding
of
promiscuity
very
limited.
Herein,
we
report
structural
mechanism
underlying
substrate
catalytic
Vibrio
dual
lipase/transferase
(VDLT).
Crystal
structures
VDLT
from
alginolyticus
(ValDLT)
its
fatty
acid
complexes
were
solved,
revealing
prominent
flexibility.
In
particular,
"Ser-His-Asp"
triad
machinery
ValDLT
contains
an
intrinsically
flexible
oxyanion
hole.
Analysis
ligand-bound
mutagenesis
showed
that
hole
other
binding
residues
undergo
distinct
conformational
changes
to
facilitate
promiscuity.
Our
study
reveals
previously
unknown
form
famous
proposes
"catalytic
site
tuning"
expand
paradigm
Accounts of Chemical Research,
Journal Year:
2021,
Volume and Issue:
54(5), P. 1209 - 1225
Published: Jan. 25, 2021
ConspectusDespite
the
astonishing
diversity
of
naturally
occurring
biocatalytic
processes,
enzymes
do
not
catalyze
many
transformations
favored
by
synthetic
chemists.
Either
nature
does
care
about
specific
products,
or
if
she
does,
has
adopted
a
different
strategy.
In
cases,
appropriate
reagents
used
chemists
are
readily
accessible
to
biological
systems.
Here,
we
discuss
our
efforts
expand
catalytic
repertoire
encompass
powerful
reactions
previously
known
only
in
small-molecule
catalysis:
formation
and
transfer
reactive
carbene
nitrene
intermediates
leading
broad
range
including
products
with
bonds
biology.
light
structural
similarity
iron
(Fe═C(R1)(R2))
(Fe═NR)
oxo
(Fe═O)
intermediate
involved
cytochrome
P450-catalyzed
oxidation,
have
precursors
that
systems
encountered
repurposed
P450s
natural
world.
The
resulting
protein
catalysts
fully
genetically
encoded
function
intact
microbial
cells
cell-free
lysates,
where
their
performance
can
be
improved
optimized
directed
evolution.
By
leveraging
promiscuity
P450
enzymes,
evolved
transferases
exhibiting
excellent
activity
toward
these
new-to-nature
reactions.
Since
initial
report
2012,
number
other
heme
proteins
myoglobins,
protoglobins,
cytochromes
c
also
been
found
engineered
promote
unnatural
transfer.
Due
altered
active-site
environments,
often
displayed
complementary
activities
selectivities
P450s.Using
wild-type
proteins,
others
described
selective
reactions,
cyclopropanation,
cyclopropenation,
Si–H
insertion,
B–H
C–H
insertion.
Similarly,
variety
asymmetric
processes
aziridination,
sulfide
imidation,
amidation,
and,
most
recently,
amination
demonstrated.
scopes
state-of-the-art
based
on
transition-metal
catalysts,
making
biocatalysts
valuable
addition
chemist's
toolbox.
Moreover,
enabled
exquisite
regio-
stereocontrol
imposed
enzyme
catalyst,
this
platform
provides
an
exciting
opportunity
address
challenging
problems
modern
chemistry
catalysis,
ones
eluded
for
decades.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Aug. 12, 2022
Regenerable
nanozymes
with
high
catalytic
stability
and
sustainability
are
promising
substitutes
for
naturally-occurring
enzymes
but
limited
by
insufficient
non-selective
activities.
Herein,
we
developed
single-atom
of
RhN
Chemical Society Reviews,
Journal Year:
2020,
Volume and Issue:
49(15), P. 5310 - 5358
Published: Jan. 1, 2020
This
review
highlights
the
developments
in
iron
and
cobalt
catalyzed
C(sp3)–H
bond
functionalization
reactions
with
emphasis
on
their
applications
organic
synthesis,
i.e.
natural
products
pharmaceuticals
synthesis
and/or
modification.
Chemical Reviews,
Journal Year:
2022,
Volume and Issue:
122(14), P. 11974 - 12045
Published: July 11, 2022
Metalloenzymes
catalyze
a
variety
of
reactions
using
limited
number
natural
amino
acids
and
metallocofactors.
Therefore,
the
environment
beyond
primary
coordination
sphere
must
play
an
important
role
in
both
conferring
tuning
their
phenomenal
catalytic
properties,
enabling
active
sites
with
otherwise
similar
environments
to
perform
diverse
array
biological
functions.
However,
since
interactions
are
numerous
weak,
it
has
been
difficult
pinpoint
structural
features
responsible
for
activities
native
enzymes.
Designing
artificial
metalloenzymes
(ArMs)
offers
excellent
basis
elucidate
roles
these
further
develop
practical
catalysts.
In
this
review,
we
highlight
how
secondary
spheres
ArMs
influence
metal
binding
catalysis,
particular
focus
on
use
protein
scaffolds
as
templates
design
by
either
rational
aided
computational
modeling,
directed
evolution,
or
combination
approaches.
describing
successes
designing
heme,
nonheme
Fe,
Cu
metalloenzymes,
heteronuclear
containing
those
other
centers
(including
non-native
ions
metallocofactors),
have
summarized
insights
gained
careful
controls
sphere,
including
hydrophobic
hydrogen
bonding
interactions,
allow
generation
respective
systems
approach,
rival,
and,
few
cases,
exceed
We
also
provided
outlook
remaining
challenges
field
future
directions
that
will
deeper
understanding
coordintion
be
gained,
turn
guide
broader
more
efficient
ArMs.
Microbial Biotechnology,
Journal Year:
2022,
Volume and Issue:
16(2), P. 195 - 217
Published: Sept. 13, 2022
Global
economies
depend
on
the
use
of
fossil-fuel-based
polymers
with
360-400
million
metric
tons
synthetic
being
produced
per
year.
Unfortunately,
an
estimated
60%
global
production
is
disposed
into
environment.
Within
this
framework,
microbiologists
have
tried
to
identify
plastic-active
enzymes
over
past
decade.
Until
now,
research
has
largely
failed
deliver
functional
biocatalysts
acting
commodity
such
as
polyethylene
(PE),
polypropylene
(PP),
polyvinylchloride
(PVC),
ether-based
polyurethane
(PUR),
polyamide
(PA),
polystyrene
(PS)
and
rubber
(SR).
However,
few
are
known
act
low-density
low-crystalline
(amorphous)
terephthalate
(PET)
ester-based
PUR.
These
above-mentioned
represent
>95%
all
plastics
produced.
Therefore,
main
challenge
currently
facing
in
finding
polymer-active
targeting
majority
plastics.
identifying
either
implement
them
biotechnological
processes
or
understand
their
potential
role
nature
emerging
field.
The
application
these
still
its
infancy.
Here,
we
summarize
current
knowledge
microbial
enzymes,
distribution
impact
plastic
degradation
industrial
nature.
We
further
outline
major
challenges
novel
optimizing
ones
by
approaches
problems
arising
through
falsely
annotated
unfiltered
database
entries.
Finally,
highlight
applications
possible
re-
upcycling
concepts
using
microorganisms.
ACS Central Science,
Journal Year:
2024,
Volume and Issue:
10(2), P. 226 - 241
Published: Feb. 5, 2024
Enzymes
can
be
engineered
at
the
level
of
their
amino
acid
sequences
to
optimize
key
properties
such
as
expression,
stability,
substrate
range,
and
catalytic
efficiency-or
even
unlock
new
activities
not
found
in
nature.
Because
search
space
possible
proteins
is
vast,
enzyme
engineering
usually
involves
discovering
an
starting
point
that
has
some
desired
activity
followed
by
directed
evolution
improve
its
"fitness"
for
a
application.
Recently,
machine
learning
(ML)
emerged
powerful
tool
complement
this
empirical
process.
ML
models
contribute
(1)
discovery
functional
annotation
known
protein
or
generating
novel
with
functions
(2)
navigating
fitness
landscapes
optimization
mappings
between
associated
values.
In
Outlook,
we
explain
how
complements
discuss
future
potential
improved
outcomes.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(27)
Published: April 24, 2024
Single-atom
nanozymes
(SAzymes)
with
atomically
dispersed
active
sites
are
potential
substitutes
for
natural
enzymes.
A
systematic
study
of
its
multiple
functions
can
in-depth
understand
SAzymes's
nature,
which
remains
elusive.
Here,
we
develop
a
novel
ultrafast
synthesis
sputtered
SAzymes
by
in
situ
bombarding-embedding
technique.
Using
this
method,
copper
(Cu)
(CuSA)
is
developed
unreported
unique
planar
Cu-C