Abstract
The
fluorinase
enzyme
(EC
2.5.1.63)
utilises
fluoride
ion
and
S‐adenosyl‐L‐methionine
(SAM)
as
substrates
for
conversion
to
5′‐fluoro‐5′‐deoxy‐adenosine
(5′‐FDA)
L‐methionine
(L‐Met).
has
a
very
strict
substrate
specificity,
however
it
been
shown
tolerate
acetylenes
NH
2
replacements
H
at
C‐2
of
the
adenine
ring
SAM.
This
tolerance
is
explored
further
here
with
−NHR,
−N
3
,
−OR
−SR
substituents
attached
C‐2.
New
activities
are
demonstrated,
example
NH‐methyl,
NH‐propyl,NH‐butyl
O‐butyl
C‐2,
azide
thioethers
were
not
tolerated.
Outcomes
supported
by
in
silico
analysis,
revealing
favourable
H‐bonding
interactions
involving
O
position
N278
backbone
amide
A279
active
site
respectively.
study
informs
on
selectivity
tool
radiolabelling
candidate
ligands
fluorine‐18
positron
emission
tomography
programmes.
Science,
Год журнала:
2024,
Номер
385(6707), С. 416 - 421
Опубликована: Июль 25, 2024
Enzymes
capable
of
assimilating
fluorinated
feedstocks
are
scarce.
This
situation
poses
a
challenge
for
the
biosynthesis
compounds
used
in
pharmaceuticals,
agrochemicals,
and
materials.
We
developed
photoenzymatic
hydrofluoroalkylation
that
integrates
motifs
into
olefins.
The
photoinduced
promiscuity
flavin-dependent
ene-reductases
enables
generation
carbon-centered
radicals
from
iodinated
fluoroalkanes,
which
directed
by
photoenzyme
to
engage
enantioselectively
with
approach
facilitates
stereocontrol
through
interaction
between
singular
unit
enzyme,
securing
high
enantioselectivity
at
β,
γ,
or
δ
positions
groups
enzymatic
hydrogen
atom
transfer-a
process
is
notably
challenging
conventional
chemocatalysis.
work
advances
strategies
integrating
chemical
opens
avenues
asymmetric
synthesis
compounds.
ACS Catalysis,
Год журнала:
2024,
Номер
14(8), С. 6358 - 6368
Опубликована: Апрель 11, 2024
Enzyme-catalyzed
stereodivergent
synthesis
to
access
all
possible
stereoisomers
of
organofluorine
compounds
bearing
multiple
stereogenic
centers
remains
an
important
and
challenging
subject.
By
integrative
data-driven
mining
mechanism-guided
engineering
ketoreductases,
we
identified
a
biocatalytic
platform
produce
four
stereoisomeric
fluoroalkyl
amino
acid
esters
two
vicinal
stereocenters.
Fast
triple-parameter
coevolution
via
semirational
CAST/ISM
strategy
provided
the
quadruple
mutant
M5
(A140K/L203T/G92A/V84I)
ketoreductase
BgADH
not
only
displayed
high
stereoselectivity
toward
target
(99:1
dr,
99%
ee)
but
also
observed
with
enhanced
activity
(kcat/Km,
6.3
folds)
improved
thermostability
(T5015,
4
°C).
Crystal
structural
analysis
molecular
dynamics
(MD)
simulation
studies
unveil
residues
(A140
F148)
be
key
sites
that
are
responsible
for
control
stereoselectivity.
The
L203T/G92A
mutation
by
affecting
conformational
distribution
α-helix
within
active-site
region,
V84I
thermal
stability
strengthening
hydrogen
bonding
network
neighboring
residues.
synthetic
utility
was
further
demonstrated
substrate
scope
expansion,
gram-scale
reactions
(648
g
L–1
day–1),
transformations
chiral
fluorinated
β-lactams
antibiotic
carbapenem
cores.
Environmental Microbiology,
Год журнала:
2022,
Номер
24(11), С. 5082 - 5104
Опубликована: Июнь 21, 2022
Abstract
The
presence
of
mineral
fluoride
(F
−
)
in
the
environment
has
both
a
geogenic
and
anthropogenic
origin,
halide
been
described
to
be
toxic
virtually
all
living
organisms.
While
evidence
gathered
different
microbial
species
supports
this
notion,
systematic
exploration
effects
F
salts
on
metabolism
physiology
environmental
bacteria
remained
underexplored
thus
far.
In
work,
we
studied
characterized
tolerance
mechanisms
deployed
by
model
soil
bacterium
Pseudomonas
putida
KT2440
against
NaF.
By
adopting
systems‐level
omic
approaches,
including
functional
genomics
metabolomics,
gauged
impact
anion
at
regulatory
levels
under
conditions
that
impair
bacterial
growth.
Several
genes
involved
were
isolated
genome‐wide
Tn
‐Seq
screening—among
which
crcB
,
encoding
an
‐specific
exporter,
was
shown
play
predominant
role
detoxification.
High‐resolution
combined
with
assessment
intracellular
extracellular
pH
values
quantitative
experiments,
underscored
key
nodes
central
carbon
affected
.
Taken
together,
our
results
indicate
P
undergoes
general,
multi‐level
stress
response
when
challenged
NaF
significantly
differs
from
caused
other
saline
stressors.
responses
oxidative
challenges
have
extensively
literature,
very
little
is
known
about
metabolism.
This
state
affairs
contrasts
fact
more
abundant
than
halides
Earth
crust
(e.g.
some
soils,
concentration
can
reach
up
1
mg
g
−1
).
Understanding
global
treatment
not
only
relevant
unveil
distinct
detoxification
but
it
could
also
guide
engineering
approaches
for
target
incorporation
fluorine
into
value‐added
organofluorine
molecules.
regard,
constitutes
ideal
explore
such
scenarios,
since
particularly
its
high
level
resistance
variety
physicochemical
perturbations.
Chemical Science,
Год журнала:
2024,
Номер
15(24), С. 9155 - 9163
Опубликована: Янв. 1, 2024
A
new
method
has
been
introduced
that
is
able
to
tackle
the
complexities
of
N–C(O)
activation
in
amide
moieties
through
utilization
pyrylium
tetrafluoroborate
a
mechanochemical
setting,
where
bonds
undergo
activation.
Current Opinion in Biotechnology,
Год журнала:
2021,
Номер
74, С. 180 - 193
Опубликована: Дек. 23, 2021
The
pressing
need
for
novel
bioproduction
approaches
faces
a
limitation
in
the
number
and
type
of
molecules
accessed
through
synthetic
biology.
Halogenation
is
widely
used
tuning
physicochemical
properties
polymers,
but
traditional
halogenation
chemistry
often
lacks
specificity
generates
harmful
by-products.
Here,
we
pose
that
deploying
metabolism
tailored
biohalogenation
represents
an
unique
opportunity
towards
economically
attractive
environmentally
friendly
organohalide
production.
On
this
background,
discuss
growth-coupled
selection
functional
metabolic
modules
harness
rich
repertoire
biosynthetic
biodegradation
capabilities
environmental
bacteria
vivo
biohalogenation.
By
rationally
combining
these
approaches,
chemical
landscape
living
cells
can
accommodate
added-value
organohalides
which,
as
today,
are
obtained
by
chemistry.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
146(29), С. 19962 - 19973
Опубликована: Июль 10, 2024
Installing
fluorine
atoms
onto
natural
products
holds
great
promise
for
the
generation
of
fluorinated
molecules
with
improved
or
novel
pharmacological
properties.
The
enzymatic
oxidative
carbon-carbon
coupling
reaction
represents
a
straightforward
strategy
synthesizing
biaryl
architectures,
but
exploration
this
method
producing
fluorine-substituted
derivatives
remains
elusive.
Here,
in
study,
we
report
protein
engineering
cytochrome
P450
from
mLife,
Год журнала:
2025,
Номер
4(2), С. 107 - 125
Опубликована: Март 28, 2025
Abstract
Biosynthesis—a
process
utilizing
biological
systems
to
synthesize
chemical
compounds—has
emerged
as
a
revolutionary
solution
21st‐century
challenges
due
its
environmental
sustainability,
scalability,
and
high
stereoselectivity
regioselectivity.
Recent
advancements
in
artificial
intelligence
(AI)
are
accelerating
biosynthesis
by
enabling
intelligent
design,
construction,
optimization
of
enzymatic
reactions
systems.
We
first
introduce
the
molecular
retrosynthesis
route
planning
biochemical
pathway
including
single‐step
algorithms
AI‐based
design
tools.
highlight
advantages
large
language
models
addressing
sparsity
data.
Furthermore,
we
review
enzyme
discovery
methods
based
on
sequence
structure
alignment
techniques.
Breakthroughs
structural
prediction
expected
significantly
improve
accuracy
discovery.
also
summarize
for
de
novo
generation
nonnatural
or
orphan
reactions,
focusing
functional
annotation
techniques
reaction
small
molecule
similarity.
Turning
engineering,
discuss
strategies
thermostability,
solubility,
activity,
well
applications
AI
these
fields.
The
shift
from
traditional
experiment‐driven
data‐driven
computationally
driven
is
already
underway.
Finally,
present
potential
provide
perspective
future
research
directions.
envision
expanded
biocatalysis
drug
development,
green
chemistry,
complex
synthesis.
