Structural and Mechanistic Characterization of the Flavin-Dependent Monooxygenase and Oxidase Involved in Sorbicillinoid Biosynthesis
ACS Chemical Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 7, 2025
Sorbicillinoids
are
yellow
secondary
metabolites
synthesized
through
an
elegant
combination
of
enzymatic
and
spontaneous
biochemical
processes.
The
flavin-dependent
monooxygenase
SorC
oxidase
SorD
crucial
in
this
interplay,
enabling
the
generation
a
diverse
array
functionally
complex
sorbicillinoids.
By
solving
crystal
structures
from
Penicillium
chrysogenum
with
sorbicillin
bound
active
site,
we
describe
catalytically
binding
conformations,
for
attaining
enantioselective
stereoselective
control
these
reactions.
structure
was
resolved
cofactor
FAD
its
out
state,
which
allowed
us
to
identify
key
residues
that
modulate
flavin
mobility
other
conformational
changes.
Catalytic
were
also
confirmed
by
detailed
characterization
wild-type
several
variants.
Meanwhile,
using
CRISPR/Cas9-based
multicopy-genome
integration
system,
could
heterologously
express
P.
Aspergillus
niger
high
yields
purity.
This
obtain
viable
catalytic
conformation.
Structural
analysis
obtained
provided
insights
into
substrate
pose
highlighted
potentially
critical
site
residues.
Ultimately,
having
both
at
our
disposal
enabled
investigate
their
functions
interplays
biosynthesis
vast
Язык: Английский
Trichodenoids A and B, Two Skeletally Unprecedented Polyketides from Trichoderma reesei with Cardioprotective Effects against H2O2-Induced Injury
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
Trichoderma
reesei,
recognized
by
the
FDA
as
a
food-safe
strain,
plays
vital
role
in
food
fermentation.
Although
enzymatic
applications
of
T.
reesei
are
well-established,
health
benefits
its
fermentation-derived
metabolites
yet
to
be
fully
explored.
Trichodenoids
A
(1)
and
B
(2),
two
skeletally
unprecedented
polyketides,
were
isolated
from
endophytic
fungus
originating
plant
Gastrodia
elata
Blume.
Their
structures
elucidated
via
spectroscopic
data,
single-crystal
X-ray
crystallographic
analysis,
quantum
chemical
DP4+
ECD
calculation.
Compounds
1
2
uniquely
defined
unusual
6/6/5
6/6/5/6
ring
systems,
respectively,
which
proposed
formed
through
key
Diels-Alder
Baeyer-Villiger
reactions
during
biosynthesis.
Compound
had
potential
mitigate
H2O2-induced
oxidative
stress
H9C2
cells
reducing
intracellular
ROS
levels,
restoring
mitochondrial
function,
regulating
mRNA
expression
related
stress,
inflammation,
autophagy.
These
findings
highlight
compound
candidate
for
natural
antioxidants
even
dietary
supplements
cardiovascular
health.
Язык: Английский
Comparative Genomic Analysis Reveals Key Changes in the Genome of Acremonium chrysogenum That Occurred During Classical Strain Improvement for Production of Antibiotic Cephalosporin C
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
26(1), С. 181 - 181
Опубликована: Дек. 28, 2024
From
the
1950s
to
present,
main
tool
for
obtaining
fungal
industrial
producers
of
secondary
metabolites
remains
so-called
classical
strain
improvement
(CSI)
methods
associated
with
multi-round
random
mutagenesis
and
screening
level
target
products.
As
a
result
application
such
techniques,
yield
in
high-yielding
(HY)
strains
was
increased
hundreds
times
compared
wild-type
(WT)
parental
strains.
However,
events
that
occur
at
molecular
during
CSI
programs
are
still
unknown.
In
this
paper,
an
attempt
made
identify
characteristic
changes
genome
occurred
Язык: Английский