bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 6, 2024
Abstract
Discovery
of
cancer
immunogenic
chemotherapeutics
represents
an
emerging,
highly
promising
direction
for
treatment
that
uses
a
chemical
drug
to
achieve
the
efficacy
both
chemotherapy
and
immunotherapy.
Herein
we
report
high-throughput
screening
platform
subsequent
discovery
new
class
chemotherapeutic
leads.
Our
integrates
informatics-based
activity
metabolomics
rapid
identification
microbial
natural
products
with
novel
structures
potent
activities.
Additionally,
demonstrate
use
microcrystal
electron
diffraction
(MicroED)
direct
structure
elucidation
lead
compounds
from
partially
purified
mixtures.
Using
this
strategy
screen
geographically
phylogenetically
diverse
metabolites
against
pseudomyxoma
peritonei,
rare
severe
cancer,
discovered
leads,
aspercyclicins.
The
aspercyclicins
feature
unprecedented
tightly
packed
polycyclic
polyketide
scaffold
comprises
continuous
fused,
bridged,
spiro
rings.
biogenesis
involves
two
distinct
biosynthetic
pathways,
leading
formation
chimeric
cannot
be
predicted
by
bottom-up
approaches
mining
genes.
With
comparable
potency
some
clinically
used
anticancer
drugs,
are
active
multiple
cell
types
inducing
death
(ICD),
including
release
damage-associated
molecular
patterns
phagocytosis
cells.
broad-spectrum
ICD-inducing
aspercyclicins,
combined
their
low
toxicity
normal
cells,
potential
particularly
first
peritonei
treatment.
Sorbicitrinol
A
(1)
and
its
biosynthetic
precursor
sorbicitrinol
B
(2),
two
novel
sorbicillinoids
with
unprecedented
skeletons,
were
isolated
from
the
sponge-derived
fungus
Penicillium
sp.
by
molecular
networking.
Their
structures
identified
spectroscopic
analyses
quantum
chemistry.
Both
of
them
exhibited
an
innovative
fusion
pattern
sorbicillinol
a
citrinin
derivative.
Compound
1
was
first
example
sorbicillinoid
featuring
unique
cage-like
2,5-dioxa-pentacyclo[10.4.03,11.04,8.04,15]tetradecane
scaffold.
Plausible
biogenetic
pathways
proposed,
their
antitumor
antifungal
activities
also
evaluated.
Chemical Communications,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
The
bifunctional
compound
V2
induced
a
VHL-dependent
NLRP3
degradation.
postulated
ternary
complex
formation
involves
the
molecular
interaction
of
(cyan)
to
binding
sites
VHL
(magenta)
and
(orange).
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
72(34), С. 19061 - 19070
Опубликована: Авг. 16, 2024
Sorbicillinoids
are
a
class
of
fungal
polyketides
with
diverse
structures
and
distinguished
bioactivities.
Although
remarkable
progress
has
been
achieved
in
their
chemistry
biosynthesis,
the
efflux
sorbicillinoids
is
poorly
understood.
Here,
we
found
MFS
transporter
AcsorT
was
responsible
for
biosynthesis
Acremonium
chrysogenum.
Combinatorial
knockout
subcellular
location
demonstrated
that
plasma
membrane-associated
transportation
sorbicillinol
subsequent
formation
oxosorbicillinol
acresorbicillinol
C
via
berberine
bridge
enzyme-like
oxidase
AcsorD
periplasm.
Homology
modeling
site-directed
mutation
revealed
Tyr303
Arg436
were
key
residues
AcsorT,
which
further
explained
by
molecular
dynamics
simulation.
Based
on
our
study,
it
suggested
modulates
sorbicillinoid
production
coordinating
its
export,
transport
model
proposed
A.
Chemical Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 1, 2025
Biosynthesis
of
penicilactam
A
(1)
reveals
a
multifunctional
P450
PnltC
catalyzing
radical
C–C
bond
cleavage
and
iminium
involved
non-radical
cyclization.
Sorbicillalanines
A
(1)
and
B
(2),
two
unusual
hybrid-sorbicillinoid
alkaloids,
were
isolated
from
Penicillium
sp.
co-cultured
with
Setosphaeria
Their
structures
containing
absolute
configurations
determined
by
detailed
spectroscopic
analysis
ECD
NMR
calculations.
Structurally,
1
2
are
the
first
sorbicillinoids
characterized
an
unprecedented
[6,5,6]-fused
ring
skeleton
a
piperidin-2-one
ring.
plausible
biosynthetic
pathway
for
was
put
forward.
displayed
significant
anti-inflammatory
activity
in
LPS-induced
RAW
264.7
macrophages.
Marine Drugs,
Год журнала:
2024,
Номер
22(8), С. 360 - 360
Опубликована: Авг. 8, 2024
Four
new
polyketides,
namely
furantides
A–B
(1–2),
talamin
E
(3)
and
arugosinacid
A
(4),
two
known
polyketides
were
obtained
from
the
mangrove-derived
fungus
Penicillium
sp.
HDN15-312
using
One
Strain
Many
Compounds
(OSMAC)
strategy.
Their
chemical
structures,
including
configurations,
elucidated
by
detailed
analysis
of
extensive
NMR
spectra,
HRESIMS
ECD.
The
DPPH
radicals
scavenging
activity
3,
with
an
IC50
value
6.79
µM,
was
better
than
vitamin
C.
Journal of the American Chemical Society,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
Cyclopentachromone,
distinguished
by
its
6/6/5
heterotricyclic
ring
structure,
is
a
key
building
block
in
many
bioactive
natural
products,
yet
enzymatic
origin
remains
unclear.
We
identified
new
class
of
cyclopentachromone-containing
compounds,
termed
isochromosulfines,
characterized
unique
C-S
bonds.
A
distinct
FAD-dependent
monooxygenase,
IscL,
was
to
catalyze
the
formation
cyclopentadiene
intermediate,
2
