Angewandte Chemie,
Journal Year:
2023,
Volume and Issue:
135(28)
Published: May 9, 2023
Abstract
The
transannular
disulfide
functions
as
a
key
structural
element
imparting
diverse
biological
activities
to
epidithiodiketopiperazines
(ETPs).
Although
mechanisms
were
proposed
in
previous
studies,
α,β′‐disulfide
formation
ETPs
is
not
well‐determined
owing
the
failure
identify
hypothetical
intermediate.
Herein,
we
characterize
ortho
‐quinone
methide
(
o
‐QM)
intermediate
and
prove
its
involvement
carbon‐sulfur
migration
from
an
α,α′‐
by
elucidating
pretrichodermamide
A
biosynthesis,
which
catalyzed
FAD‐dependent
thioredoxin
oxygenase
TdaE
harboring
noncanonical
CXXQ
motif.
Biochemical
investigations
of
recombinant
mutants
demonstrated
that
construction
was
initiated
Gln140
triggering
proton
abstraction
for
generation
essential
‐QM
intermediate,
accompanied
β′‐acetoxy
elimination.
Subsequent
attack
on
α,α′‐disulfide
Cys137
led
spirofuran
formation.
This
study
expands
biocatalytic
toolbox
sets
stage
targeted
discovery
bioactive
ETPs.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(28)
Published: May 9, 2023
Abstract
The
transannular
disulfide
functions
as
a
key
structural
element
imparting
diverse
biological
activities
to
epidithiodiketopiperazines
(ETPs).
Although
mechanisms
were
proposed
in
previous
studies,
α,β′‐disulfide
formation
ETPs
is
not
well‐determined
owing
the
failure
identify
hypothetical
intermediate.
Herein,
we
characterize
ortho
‐quinone
methide
(
o
‐QM)
intermediate
and
prove
its
involvement
carbon‐sulfur
migration
from
an
α,α′‐
by
elucidating
pretrichodermamide
A
biosynthesis,
which
catalyzed
FAD‐dependent
thioredoxin
oxygenase
TdaE
harboring
noncanonical
CXXQ
motif.
Biochemical
investigations
of
recombinant
mutants
demonstrated
that
construction
was
initiated
Gln140
triggering
proton
abstraction
for
generation
essential
‐QM
intermediate,
accompanied
β′‐acetoxy
elimination.
Subsequent
attack
on
α,α′‐disulfide
Cys137
led
spirofuran
formation.
This
study
expands
biocatalytic
toolbox
sets
stage
targeted
discovery
bioactive
ETPs.
Frontiers in Microbiology,
Journal Year:
2025,
Volume and Issue:
16
Published: Feb. 12, 2025
Introduction
Vegetation
degradation
and
soil
erosion
are
severe
problems
in
the
Loess
hilly
region,
rendering
it
one
of
most
ecologically
vulnerable
areas
China
globally.
restoration
has
been
recognized
as
an
effective
approach
to
amending
fragile
ecological
environment
restoring
degraded
ecosystems.
Methods
The
effects
different
vegetation
types:
Caragana
korshinskii,
Prunus
armeniaca
L.,
Pinus
tabuliformis
Carrière,
Medicago
sativa
control
Stipa
bungeana
on
micro-food
webs
multifunctionality,
well
their
response
mechanisms
environmental
drivers,
were
investigated
using
High-throughput
sequencing
technology.
Results
C.
korshinskii
significantly
enhanced
physicochemical
properties
enzyme
activities
by
facilitating
stability
web
structure
driven
bacteria
fungi
increasing
multifunctionality
contrast
S.
.
also
improved
promoting
organic
carbon
alkaline
phosphatase
activity.
However,
suboptimal
P.
M.
Soil
pH,
along
with
carbon,
nitrogen,
phosphorus
cycling
nutrients
enzymes,
profoundly
influences
multifunctionality;
among
these
factors,
those
related
cycles
identified
key
influencing
factors.
Discussion
Therefore,
a
strategy
prioritizing
dominant
type,
supplemented
,
impacts
stabilizing
hill
regions
comparable
areas.
Antioxidants,
Journal Year:
2025,
Volume and Issue:
14(3), P. 330 - 330
Published: March 11, 2025
Worldwide,
lung
cancer
is
the
most
common
cause
of
cancer-related
death,
which
made
worse
by
development
drug
resistance
during
treatment.
It
urgent
to
develop
new
therapeutic
methods
and
small
molecule
drugs
for
tumor
resistance.
Chaetocin,
extracted
from
Chaetomium
minutum,
a
natural
compound
with
good
antitumor
activity.
However,
there
are
few
studies
on
its
In
this
paper,
firstly,
chaetotocin
significantly
inhibited
viability
migration
cisplatin-resistant
non-small
cell
(NSCLC)
cells
xenograft
growth
nude
mice.
Chaetocin
at
4
mg/kg
A549/DDP
an
inhibition
rate
70.43%.
Subsequently,
underlying
mechanism
behind
actions
chaetocin
was
explored.
discovered
that
can
inhibit
transketolase
(TKT),
thereby
inhibiting
NSCLC
inducing
death.
Compared
cisplatin-sensitive
cells,
lower
concentration
cisplatin-resistance
migration.
Mechanistically,
TKT
identified
as
potential
target
chaetocin.
The
KD
value
interaction
between
63.2
μM.
An
amount
0.2
μM
may
suppress
enzyme
activity
expression
level
TKT.
We
found
higher
in
further
explains
why
these
were
more
vulnerable
terms
phenotype.
Additionally,
muti-omics
analysis
RNA
interference
suggested
PI3K/Akt
signaling
pathway
through
conclusion,
could
directly
bind
TKT,
expression,
interfered
intracellular
metabolism
oxidation-reduction
balance,
then
regulated
induce
apoptosis.
Journal of Fungi,
Journal Year:
2025,
Volume and Issue:
11(4), P. 241 - 241
Published: March 22, 2025
Epidithiodiketopiperazines
(ETPs)
are
a
class
of
fungal
secondary
metabolites
(SMs)
featuring
transannular
disulfide
bridge
at
the
diketopiperazine
(DKP)
core.
The
complex
structures
and
biological
activities
have
attracted
widespread
attention
from
biologists
chemists.
In
this
study,
we
identified
five
novel
ETP
derivatives
4–7
4′
three
gene
deletion
mutants
Trichoderma
hypoxylon
CGMCC
3.17906,
including
ΔtdaP,
ΔtdaQ,
ΔtdaQΔtdaI.
Their
were
characterized
through
NMR
HR-ESI-MS
data
analysis.
Compounds
4
unique
heteroatom
substitutions
α
α′
positions,
compound
5
possesses
α,
β′-disulfide
bridge,
compounds
6
7
contain
C3′-(thio)carbonyl
group.
Based
on
structural
elucidation
biosynthetic
pathway
bridged
ETPs,
also
proposed
formation
4′.
This
study
not
only
expands
chemical
diversity
but
offers
new
mechanistic
insights
into
pathways
ETPs.
Natural Product Reports,
Journal Year:
2023,
Volume and Issue:
40(12), P. 1874 - 1900
Published: Jan. 1, 2023
This
review
summarizes
the
chemical
family
of
natural
products
with
1,2-oxazine
scaffold,
focusing
on
their
source
organisms,
structural
diversities,
bioactivities,
synthesis,
and
biosynthesis.
Advanced Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 28, 2024
Abstract
Microbial
genetic
circuits
are
vital
for
regulating
gene
expression
and
synthesizing
bioactive
compounds.
However,
assessing
their
strength
timing,
especially
in
multicellular
fungi,
remains
challenging.
Here,
an
advanced
microfluidic
platform
is
combined
with
a
mathematical
model
enabling
precise
characterization
of
fungal
regulatory
(GRCs)
at
the
single‐cell
level.
Utilizing
this
platform,
intensity
timing
30
transcription
factor‐promoter
combinations
derived
from
two
representative
GRCs,
using
fungus
Aspergillus
nidulans
determined.
As
proof
concept,
selected
GRC
combination
utilized
to
successfully
refactor
biosynthetic
pathways
molecules,
precisely
control
production,
activate
silenced
clusters
(BGCs).
This
study
provides
insights
into
microbial
regulation
highlights
potential
synthetic
biology
applications
discovery
novel
natural
products.
