Frontiers in Marine Science,
Journal Year:
2025,
Volume and Issue:
11
Published: Jan. 21, 2025
The
microbial
diversity
in
oceans
is
considerable,
widely
distributed
seawater,
marine
sediments,
and
organisms.
Compared
with
terrestrial
resources
traditional
natural
product
research,
the
living
environments
of
microorganisms
are
starkly
different.
drastic
differences
survival
conditions,
such
as
high
salinity,
oligotrophic
lack
light,
limited
oxygen,
determine
that
exhibit
distinctive
characteristics
metabolism,
modes,
adaptive
mechanisms.
These
factors
contribute
to
significant
distinctions
secondary
metabolic
pathways
enzymatic
reaction
mechanisms
between
microorganisms.
In
this
review,
we
summarized
a
total
72
novel
products
antibacterial
activity,
published
2024,
which
derived
from
marine-derived
fungi.
(polyketides,
alkaloids,
terpenoids,
peptides)
emphasized
terms
their
structures
biological
activities.
This
article
aims
provide
useful
information
for
research
development
antibiotics.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(8), P. 5377 - 5396
Published: April 5, 2023
We
have
analyzed
FDA-approved
macrocyclic
drugs,
clinical
candidates,
and
the
recent
literature
to
understand
how
macrocycles
are
used
in
drug
discovery.
Current
drugs
mainly
infectious
disease
oncology,
while
oncology
is
major
indication
for
candidates
Most
bind
targets
that
difficult
binding
sites.
Natural
products
provided
80–90%
of
whereas
ChEMBL
less
complex
structures.
Macrocycles
usually
reside
beyond
Rule
5
chemical
space,
but
30–40%
orally
bioavailable.
Simple
bi-descriptor
models,
i.e.,
HBD
≤
7
combination
with
either
MW
<
1000
Da
or
cLogP
>
2.5,
distinguished
orals
from
parenterals
can
be
as
filters
design.
propose
breakthroughs
conformational
analysis
inspiration
natural
will
further
improve
de
novo
design
macrocycles.
Journal of Medicinal Chemistry,
Journal Year:
2023,
Volume and Issue:
66(8), P. 5305 - 5331
Published: April 4, 2023
Chlorine
is
one
of
the
most
common
atoms
present
in
small-molecule
drugs
beyond
carbon,
hydrogen,
nitrogen,
and
oxygen.
There
are
currently
more
than
250
FDA-approved
chlorine-containing
drugs,
yet
beneficial
effect
chloro
substituent
has
not
been
reviewed.
The
seemingly
simple
substitution
a
hydrogen
atom
(R
=
H)
with
chlorine
Cl)
can
result
remarkable
improvements
potency
up
to
100,000-fold
lead
profound
effects
on
pharmacokinetic
parameters
including
clearance,
half-life,
drug
exposure
vivo.
Following
literature
terminology
"magic
methyl
effect"
term
coined
herein.
Although
reports
500-fold
or
1000-fold
often
serendipitous
discoveries
that
be
considered
"magical"
rather
planned,
hypotheses
made
explain
magic
lessons
accelerate
cycle
discovery.
JACS Au,
Journal Year:
2023,
Volume and Issue:
3(3), P. 715 - 735
Published: Feb. 27, 2023
Biocatalysis
is
a
highly
valued
enabling
technology
for
pharmaceutical
research
and
development
as
it
can
unlock
synthetic
routes
to
complex
chiral
motifs
with
unparalleled
selectivity
efficiency.
This
perspective
aims
review
recent
advances
in
the
implementation
of
biocatalysis
across
early
late-stage
focus
on
processes
preparative-scale
syntheses.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(36)
Published: June 17, 2024
Abstract
This
review
analyzes
a
development
in
biochemistry,
enzymology
and
biotechnology
that
originally
came
as
surprise.
Following
the
establishment
of
directed
evolution
stereoselective
enzymes
organic
chemistry,
concept
partial
or
complete
deconvolution
selective
multi‐mutational
variants
was
introduced.
Early
experiments
led
to
finding
mutations
can
interact
cooperatively
antagonistically
with
one
another,
not
just
additively.
During
past
decade,
this
phenomenon
shown
be
general.
In
some
studies,
molecular
dynamics
(MD)
quantum
mechanics/molecular
mechanics
(QM/MM)
computations
were
performed
order
shed
light
on
origin
non‐additivity
at
all
stages
an
evolutionary
upward
climb.
Data
used
construct
unique
multi‐dimensional
rugged
fitness
pathway
landscapes,
which
provide
mechanistic
insights
different
from
traditional
landscapes.
Along
related
line,
biochemists
have
long
tested
result
introducing
two
point
enzyme
for
reasons,
followed
by
comparison
respective
double
mutant
so‐called
cycles,
showed
only
additive
effects,
but
more
recently
also
uncovered
cooperative
antagonistic
non‐additive
effects.
We
conclude
suggestions
future
work,
call
unified
overall
picture
epistasis.
JACS Au,
Journal Year:
2023,
Volume and Issue:
3(5), P. 1267 - 1283
Published: May 4, 2023
Enzymes
have
firmly
established
themselves
as
bespoke
catalysts
for
small
molecule
transformations
in
the
pharmaceutical
industry,
from
early
research
and
development
stages
to
large-scale
production.
In
principle,
their
exquisite
selectivity
rate
acceleration
can
also
be
leveraged
modifying
macromolecules
form
bioconjugates.
However,
available
face
stiff
competition
other
bioorthogonal
chemistries.
this
Perspective,
we
seek
illuminate
applications
of
enzymatic
bioconjugation
an
expanding
palette
new
drug
modalities.
With
these
applications,
wish
highlight
some
examples
current
successes
pitfalls
using
enzymes
along
pipeline
try
illustrate
opportunities
further
development.
ACS Central Science,
Journal Year:
2024,
Volume and Issue:
10(3), P. 519 - 528
Published: Feb. 14, 2024
Research
into
natural
products
emerged
from
humanity's
curiosity
about
the
nature
of
matter
and
its
role
in
materia
medica
diverse
civilizations.
Plants
fungi,
particular,
supplied
materials
that
altered
behavior,
perception,
well-being
profoundly.
Many
active
principles
remain
well-known
today:
strychnine,
morphine,
psilocybin,
ephedrine.
The
potential
to
circumvent
constraints
supply
explore
properties
these
led
field
product
synthesis.
This
research
delivered
new
molecules
with
properties,
but
also
fundamental
insights
chemistry
nonmetal
elements
H,
C,
N,
O,
P,
S,
Se,
their
combinations,
i.e.,
organic
chemistry.
It
a
potent
culture
focused
on
bigger
races
finish
line,
perhaps
at
expense
actionable
next
steps.
About
20
years
ago,
began
contract
United
States.
solely
chemical
reaction
development,
especially
catalysis,
filled
void.
After
all,
reactions
mechanistic
insight
could
be
immediately
implemented
by
community,
so
it
became
hard
justify
lengthy
procurement
complex
molecule
sat
freezer
unused.
shift
coincided
divestment
portfolios
pharmaceutical
companies
an
emphasis
academic
applications-driven
research,
more
science.
However,
as
bioassays
tools
biology
become
widespread,
synthesis
finds
powerful
ally
allows
us
better
deliver
premise
field.
And
hard-won
can
encoded
digitally,
mined
data
science,
applied
challenges,
chemists
perturb
even
surpass
products.
21st
century
promises
developments,
both
interface
biology,
if
community
scientists
fosters
growth.
essay
tries
contextualize
for
broad
audience,
looks
ahead
transformation
coming
years,
expects
future
bright.
JACS Au,
Journal Year:
2024,
Volume and Issue:
4(4), P. 1591 - 1604
Published: April 9, 2024
P450
NascB
catalyzes
the
coupling
of
cyclo-(l-tryptophan-l-proline)
(1)
to
generate
(−)-naseseazine
C
(2)
through
intramolecular
C–N
bond
formation
and
intermolecular
C–C
coupling.
A
thorough
understanding
its
catalytic
mechanism
is
crucial
for
engineering
or
design
P450-catalyzed
dimerization
reactions.
By
employing
MD
simulations,
QM/MM
calculations,
enhanced
sampling,
we
assessed
various
mechanisms
from
recent
works.
Our
study
demonstrates
that
most
favorable
pathway
entails
transfer
a
hydrogen
atom
N7–H
Cpd
I.
Subsequently,
there
conformational
change
in
substrate
radical,
shifting
it
Re-face
Si-face
N7
Substrate
1.
The
conformation
1
stabilized
by
protein
environment
π–π
stacking
interaction
between
indole
ring
heme
porphyrin.
subsequent
C3–C6′
radical
2
occurs
via
attack
mechanism.
switch
not
only
lowers
barrier
but
also
yields
correct
stereoselectivity
observed
experiments.
In
addition,
evaluated
reactivity
ferric-superoxide
species,
showing
reactive
enough
initiate
abstraction
NH
group
substrate.
simulation
provides
comprehensive
mechanistic
insight
into
how
enzyme
precisely
controls
both
cyclization
current
findings
align
with
available
experimental
data,
emphasizing
pivotal
role
dynamics
governing
catalysis.