ACS Bio & Med Chem Au,
Год журнала:
2024,
Номер
5(1), С. 16 - 30
Опубликована: Ноя. 27, 2024
Cytochrome
P450
enzymes
catalyze
a
large
number
of
oxidative
transformations
that
are
responsible
for
natural
product
synthesis.
Recent
studies
have
revealed
their
unique
ability
to
the
formation
C-N
and
C-S
bonds,
broadening
biosynthetic
applications.
However,
enzymatic
mechanisms
behind
these
reactions
still
unclear.
This
review
focuses
on
theoretical
insights
into
P450-catalyzed
bond
formation.
The
key
roles
conformational
dynamics
substrate
radicals,
influenced
by
enzyme
environment,
in
modulating
selectivity
reactivity
highlighted.
Understanding
reaction
offers
valuable
guidance
engineering
design
Abstract
The
C−C
or
C−N
bond
formation
is
critical
in
the
synthesis
of
pharmaceuticals
and
other
value‐added
products;
however,
traditional
metal‐catalysed
has
brought
about
environmental
resource
issues.
A
plethora
engineered
heme‐dependent
enzymes,
such
as
cytochrome
P450,
have
exhibited
enormous
potential
biocatalysis
for
formation.
With
development
computational
spectroscopic
methods,
mechanisms
underlying
heme‐catalysed
been
extensively
investigated.
In
presence
carbene
nitrene
precursor,
an
active
iron
porphyrin
(
IPC
)
IPN
formed,
which
subsequently
reacts
with
a
second
substrate
to
form
new
bonds.
Apart
from
widely
studied
/
‐facilitated
catalytic
pathway,
halide‐initiated
radical
cyclization
pathway
Cpd‐I‐catalysed
diradical
also
proposed.
These
mechanistic
insights
enabled
rational
engineering
de
novo
design
heme
enzymes.
This
review
summarises
recent
advances
enzymatic
presents
successful
applications
mechanism‐based
enzyme
design.
It
would
shed
light
on
tailored
biocatalysts
complex
but
valuable
industrial
products.
Fermentation,
Год журнала:
2024,
Номер
10(12), С. 604 - 604
Опубликована: Ноя. 26, 2024
Hydroxylation
reaction
is
a
significant
source
of
structural
diversity
in
natural
products
(NPs),
playing
crucial
role
improving
the
bioactivity,
solubility,
and
stability
product
molecules.
This
review
summarizes
latest
research
progress
field
hydroxylation,
focusing
on
several
key
hydroxylases
involved
biosynthesis
NPs,
including
cytochrome
P450
monooxygenases,
α-ketoglutarate-dependent
hydroxylases,
flavin-dependent
monooxygenases.
These
enzymes
achieve
selective
hydroxylation
modification
various
such
as
terpenoids,
flavonoids,
steroids,
through
different
catalytic
mechanisms.
systematically
recent
advances
amino
acids,
lipids,
phenylpropanoids,
demonstrating
potential
synthetic
biology
strategies
constructing
artificial
biosynthetic
pathways
producing
hydroxylated
derivatives.
Through
metabolic
engineering,
enzyme
genetic
combined
with
intelligence-assisted
technologies,
series
engineered
strains
have
been
successfully
constructed
for
efficient
production
NPs
their
derivatives,
achieving
synthesis
NPs.
has
provided
new
avenues
drug
development,
functional
food,
biomaterial
also
offered
ideas
industrial
these
compounds.
In
future,
integrating
pathway
design,
directed
evolution,
dynamic
regulation,
intelligence
technology
expected
to
further
expand
application
enzyme-catalyzed
reactions
green
complex
promoting
heights.
ACS Bio & Med Chem Au,
Год журнала:
2024,
Номер
5(1), С. 16 - 30
Опубликована: Ноя. 27, 2024
Cytochrome
P450
enzymes
catalyze
a
large
number
of
oxidative
transformations
that
are
responsible
for
natural
product
synthesis.
Recent
studies
have
revealed
their
unique
ability
to
the
formation
C-N
and
C-S
bonds,
broadening
biosynthetic
applications.
However,
enzymatic
mechanisms
behind
these
reactions
still
unclear.
This
review
focuses
on
theoretical
insights
into
P450-catalyzed
bond
formation.
The
key
roles
conformational
dynamics
substrate
radicals,
influenced
by
enzyme
environment,
in
modulating
selectivity
reactivity
highlighted.
Understanding
reaction
offers
valuable
guidance
engineering
design
