Angewandte Chemie,
Год журнала:
2023,
Номер
135(52)
Опубликована: Ноя. 14, 2023
Abstract
Die
Diterpensynthase
AlTS
aus
Aspergillus
luchuensis
wurde
identifiziert.
katalysiert
die
Bildung
des
Diterpenkohlenwasserstoffs
Spiroluchuen
A,
der
ein
neuartiges
Gerüst
aufweist,
das
durch
spirocyclisches
Ringsystem
gekennzeichnet
ist.
Der
Cyclisierungsmechanismus
zu
dieser
Verbindung
Isotopenmarkierungsexperimente
in
mit
DFT‐Berechnungen
und
metadynamischen
Simulationen
aufgeklärt.
Das
biosynthetische
Zwischenprodukt
Luchudien
neben
dem
Derivat
B
einer
Enzymvariante
abgefangen,
ortsspezifische
Mutagenese
erhalten
wurde.
Mit
seinem
10‐gliedrigen
Ring
ist
strukturell
Germacrenen
verwandt
kann
eine
Cope‐Umlagerung
Luchuelemen
eingehen.
Journal of Natural Products,
Год журнала:
2024,
Номер
87(2), С. 195 - 206
Опубликована: Янв. 24, 2024
Terpenoids,
the
largest
and
most
structurally
diverse
natural
product
family,
are
predominantly
found
in
fungi
plants,
with
bacterial
terpenoids
forming
a
minor
fraction.
Here,
we
established
an
efficient
platform
that
integrates
genome
mining
NMR-tracking
for
prioritizing
strains
tracking
terpenoids.
By
employing
this
platform,
selected
Journal of Fungi,
Год журнала:
2024,
Номер
10(5), С. 350 - 350
Опубликована: Май 13, 2024
Sesquiterpenoids
served
as
an
important
source
for
natural
product
drug
discovery.
Although
genome
mining
approaches
have
revealed
numerous
novel
sesquiterpenoids
and
biosynthetic
enzymes,
the
comprehensive
landscape
of
fungal
sesquiterpene
synthases
(STSs)
remains
elusive.
In
this
study,
123
previously
reported
STSs
were
subjected
to
phylogenetic
analysis,
resulting
in
identification
a
fungi-specific
STS
family
known
trichodiene
synthase-like
(TDTSs).
Subsequently,
application
hidden
Markov
models
allowed
discovery
517
TDTSs
from
our
in-house
fungi
library
over
400
sequenced
genomes,
these
defined
into
79
families
based
on
sequence
similarity
network.
Based
novelty
protein
sequences
completeness
their
gene
clusters,
23
TDTS
genes
selected
heterologous
expression
Aspergillus
oryzae.
total,
10
active
collectively
produced
12
mono-
sesquiterpenes,
first
chamipinene
synthase,
well
fungi-derived
cedrene,
sabinene,
camphene
synthases.
Additionally,
with
guidance
functionally
characterized
TDTSs,
we
found
that
Family
1
could
produce
bridged-cyclic
while
those
2
synthesize
spiro-
sesquiterpenes.
Our
research
presents
new
avenue
sesquiterpenoids.
Journal of Natural Products,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 30, 2025
A
bioassay-guided
chemical
investigation
of
the
endophytic
fungus
Chaetomium
nigricolor
F5
resulted
in
discovery
two
novel
sesquiterpenes,
chamilactones
and
B
(1
2),
with
a
new
9,10-seco-15-nor-isoilludalane
carbon
skeleton,
together
several
biosynthetically
related
precursors
(3-8).
Their
structures
absolute
configurations
were
elucidated
by
analysis
MS,
NMR,
calculated
13C
shifts,
ECD
calculations,
single-crystal
X-ray
diffraction
data.
It
was
proposed
that
an
unprecedented
carbon-carbon
bond
cleavage
between
C-9
C-10
3-8
key
step
biosynthetic
pathway
1
2.
Compound
3
displayed
potent
neuroprotective
effects
reducing
phosphorylation
level
p65
inhibiting
its
nuclear
translocation
TLR4-mediated
NF-κB
signaling
LPS-induced
BV2
microglial
cells.
Pharmaceutics,
Год журнала:
2025,
Номер
17(3), С. 315 - 315
Опубликована: Март 1, 2025
Chinese
materia
medica
(CMM)
refers
to
the
medicinal
substances
used
in
traditional
medicine.
In
recent
years,
CMM
has
become
globally
prevalent,
and
scientific
research
on
increasingly
garnered
attention.
Computer-aided
drug
design
(CADD)
been
employed
Western
medicine
for
many
contributing
significantly
its
progress.
However,
role
of
CADD
not
systematically
reviewed.
This
review
briefly
introduces
methods
from
perspectives
computational
chemistry
(including
quantum
chemistry,
molecular
mechanics,
mechanics/molecular
mechanics)
informatics
cheminformatics,
bioinformatics,
data
mining).
Then,
it
provides
an
exhaustive
discussion
applications
these
through
rich
cases.
Finally,
outlines
advantages
challenges
research.
conclusion,
despite
current
challenges,
still
offers
unique
over
experiments.
With
development
industry
computer
science,
especially
driven
by
artificial
intelligence,
is
poised
play
pivotal
advancing
Journal of the American Chemical Society,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 12, 2025
Sesquiterpene
synthases
(STSs)
catalyze
carbocation
cascade
reactions
with
various
hydrogen
shifts
and
cyclization
patterns
that
generate
structurally
diverse
sesquiterpene
skeletons.
However,
the
molecular
basis
for
cyclizations,
which
determine
STS
product
distributions,
remains
enigmatic.
In
this
study,
an
elusive
SydA
was
identified
in
biosynthesis
of
sydonol,
synthesized
a
new
bisabolene-type
6
unique
saturated
terminal
pendant
isopentane.
Extensive
evidence
from
isotope
labeling
experiments,
crystal
structures
its
variant,
quantum
chemical
calculations,
mutagenesis
experiments
reveal
plausible
mechanism
formation
involving
unusual
1,7-hydride
shift,
may
be
key
branchpoint
monocyclic,
bicyclic,
tricyclic
products.
Structure-based
engineering
resulted
variants
promote
different
reaction
pathways,
leading
to
production
bicyclic
α-cuprenene
(+)-β-chamigrene
7-epi-β-cedrene
β-microbiotene.
These
findings
not
only
bisabolene
but
also
provide
insights
into
hydride
pave
way
STSs
produce
complex
terpenoid
Journal of Chemical Information and Modeling,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 13, 2025
Artemisinin
(Qinghaosu)
is
an
important
antimalaria
natural
medicine
containing
a
unique
endoperoxide
bridge
in
its
sesquiterpene
structure.
The
last
phase
of
artemisinin
biosynthesis
involves
conversion
dihydroartemisinic
acid
(DHAA)
to
artemisinin,
and
the
detailed
mechanism
remains
unclear.
Based
on
previous
experimental
studies,
this
work
investigated
possible
nonenzymatic
DHAA
identified
most
chemically
plausible
reaction
pathway
using
quantum
chemical
computations.
rate-determining
step
acid-catalyzed
oxidation
enol
by
triplet
O2,
with
overall
free
energy
barrier
22.5
kcal/mol.
This
also
gives
byproducts
dihydroarteannuin
B
dihydro-epi-arteannuin
B.
In
addition,
formation
21
products
from
Artemisia
annua
was
discussed
work.
These
results
provide
fundamental
knowledge
biosynthetic
processes
related
products,
as
well
references
for
semisynthesis
structural
modification
studies
artemisinin.
