Journal of Natural Products,
Journal Year:
2024,
Volume and Issue:
87(10), P. 2384 - 2392
Published: Sept. 27, 2024
Secondary
metabolites
are
generally
produced
by
enzymes
encoded
genes
within
a
biosynthetic
gene
cluster.
Transcription
factor
frequently
located
these
clusters.
These
transcription
factors
often
drive
expression
of
the
other
cluster,
and
overexpression
provides
facile
approach
to
express
all
resulting
in
production
downstream
metabolite(s).
Unfortunately
this
is
not
always
successful,
leading
us
engineer
more
effective
hybrid
factors.
Herein,
we
attempted
activate
putative
cryptic
cluster
Frontiers in Natural Products,
Journal Year:
2024,
Volume and Issue:
3
Published: Feb. 12, 2024
Peptide
natural
products
have
a
wide
range
of
useful
applications
as
pesticides,
veterinary
agents,
pharmaceuticals,
and
bioproducts.
To
discover
new
products,
manipulate
them
for
analog
generation,
to
harness
the
potential
these
bioactive
compounds
synthetic
biology,
it
is
necessary
develop
robust
methods
expression
biosynthetic
genes.
Cell-free
biology
emerging
an
important
complementary
approach
because
highly
desirable
express
protein
on
more
rapid
timescale
does
not
rely
upon
genetic
tractability
strain
thus
improving
throughput
design-build-test-learn
cycles.
Additionally,
generating
metabolites
outside
cell
can
overcome
issues
such
cellular
toxicity
which
hamper
like
antibiotic
development.
In
this
review,
we
focus
cell-free
production
peptide
generated
by
non-ribosomal
synthetase.
Nonribsomal
peptides
are
biosynthesized
synthetases
large
“mega”
enzymes
that
provide
specific
challenges
heterologous
expression.
First,
summarize
NRPSs
their
corresponding
expressed
in
systems.
With
that,
discuss
requirements
proteins
synthesis
well
host
machineries
been
developed
could
be
particularly
relevant
future.
The
development
systems
then
used
prototyping
accelerate
efforts
towards
engineered
biosynthesis
complex
pathways.
Applied Microbiology and Biotechnology,
Journal Year:
2024,
Volume and Issue:
108(1)
Published: July 24, 2024
Abstract
Filamentous
fungi
are
prolific
producers
of
bioactive
natural
products
and
play
a
vital
role
in
drug
discovery.
Yet,
their
potential
cannot
be
fully
exploited
since
many
biosynthetic
genes
silent
or
cryptic
under
laboratory
culture
conditions.
Several
strategies
have
been
applied
to
activate
these
genes,
with
heterologous
expression
as
one
the
most
promising
approaches.
However,
successful
identification
new
often
hindered
by
host-dependent
factors,
such
low
gene
targeting
efficiencies,
high
metabolite
background,
lack
selection
markers.
To
overcome
challenges,
we
constructed
Penicillium
crustosum
host
pyrG
deficient
strain
combining
split-marker
strategy
CRISPR-Cas9
technology.
Deletion
ligD
pcribo
improved
efficiencies
enabled
use
an
additional
marker
P.
.
Furthermore,
reduced
secondary
background
inactivation
two
highly
expressed
clusters
abolished
formation
reactive
ortho
-quinone
methide.
Finally,
replaced
pigment
pcr4401
commonly
used
Aspergillus
nidulans
wA
site
for
convenient
constructs
originally
designed
A.
our
strain.
As
proof
concept,
successfully
single
polyketide
synthase
entire
cluster
at
locus.
Resulting
transformants
were
easily
detected
albino
phenotype.
With
this
study,
provide
efficient
platform
fungal
genes.
Key
points
Construction
Reduction
genetic
dereplication
Integration
alternative
besides
Graphical
Journal of Fungi,
Journal Year:
2024,
Volume and Issue:
10(4), P. 266 - 266
Published: April 2, 2024
In
1999,
the
first
biosynthetic
gene
cluster
(BGC),
synthesizing
virulence
factor
DHN
melanin,
was
characterized
in
Aspergillus
fumigatus.
Since
then,
19
additional
BGCs
have
been
linked
to
specific
secondary
metabolites
(SMs)
this
species.
Here,
we
provide
a
comprehensive
timeline
of
A.
fumigatus
BGC
discovery
and
find
that
initial
advances
centered
around
commonly
expressed
SMs
where
chemical
structure
informed
rationale
identification
producing
(e.g.,
gliotoxin,
fumigaclavine,
fumitremorgin,
pseurotin
A,
helvolic
acid,
fumiquinazoline).
Further
followed
transcriptional
profiling
ΔlaeA
mutant,
which
aided
endocrocin,
fumagillin,
hexadehydroastechrome,
trypacidin,
fumisoquin
BGCs.
These
their
precursors
are
produced
most
studies.
Characterization
other
BGC/SM
pairs
required
efforts,
such
as
induction
treatments,
including
co-culture
with
bacteria
(fumicycline/neosartoricin,
fumigermin)
or
growth
under
copper
starvation
(fumivaline,
fumicicolin).
Finally,
four
were
discovered
via
overexpression
technologies,
use
heterologous
hosts
fumihopaside,
sphingofungin,
sartorypyrone).
Initial
analysis
two
studied
isolates,
Af293
A1160,
suggested
both
harbored
ca.
34–36
However,
an
examination
264
available
genomes
shows
up
20
BGCs,
some
strains
showing
considerable
variations
number
composition.
new
present
frontier
future
metabolism
characterization
important
Research Square (Research Square),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 20, 2025
Abstract
Fungal
natural
products,
including
polyketides,
are
a
rich
source
of
bioactive
molecules.
Their
biosynthetic
enzymes
encoded
within
gene
clusters,
which
often
activated
by
specific
environmental
conditions.
As
result,
many
products
not
produced
under
standard
laboratory
Heterologous
expression
bypasses
native
regulation,
enabling
systematic
approach
for
polyketide
discovery.
The
most
widely
used
fungal
hosts
product
production
Saccharomycetales
yeasts,
and
filamentous
Eurotiomycetes.
Yeasts
highly
tractable
but
have
narrow
scope
due
to
their
limited
secondary
metabolism,
while
Eurotiomycetes
richer
metabolism
more
difficult
engineer.
In
this
work,
we
established
two
yeasts
the
genera
Exophiala
and
Knufia
as
novel
heterologous
broad
range
polyketides.
These
combine
genetic
tractability
yeast
with
metabolic
robustness
fungi.
We
developed
engineering
tools
precise
integration
genome
editing,
allowing
us
heterologously
express
five
synthases
different
domain
architectures,
one
involved
in
biosynthesis
previously
undescribed
2-pyridone.
Our
findings
demonstrate
that
these
can
efficiently
produce
complex
paving
way
synthase
engineering.
Journal of Natural Products,
Journal Year:
2024,
Volume and Issue:
87(7), P. 1704 - 1713
Published: July 11, 2024
Fungal
secondary
metabolite
(SM)
biosynthetic
gene
clusters
(BGCs)
containing
dimethylallyltryptophan
synthases
(DMATSs)
produce
structurally
diverse
prenylated
indole
alkaloids
with
wide-ranging
activities
that
have
vast
potential
as
human
therapeutics.
To
discover
new
natural
products
produced
by
DMATSs,
we
mined
the
Department
of
Energy
Joint
Genome
Institute's
MycoCosm
database
for
DMATS-containing
BGCs.
We
found
a
DMATS
BGC
in
Natural Product Reports,
Journal Year:
2023,
Volume and Issue:
40(12), P. 1816 - 1821
Published: Jan. 1, 2023
A
personal
selection
of
32
recent
papers
is
presented
covering
various
aspects
current
developments
in
bioorganic
chemistry
and
novel
natural
products
such
as
alscholarine
from
Organics,
Journal Year:
2023,
Volume and Issue:
4(4), P. 539 - 561
Published: Dec. 15, 2023
4-Hydroxy-2-pyrones
are
of
interest
as
potential
biorenewable
molecules
for
a
sustainable
transition
from
biomass
feedstock
to
valuable
chemical
products.
This
review
focuses
on
the
methodologies
synthesis
4-hydroxy-2-pyrones
published
over
last
20
years.
These
pyrones
polyketides
widespread
in
Nature
and
possess
versatile
bioactivity
that
makes
them
an
attractive
target
modification.
Biosynthetic
paths
actively
developed
used
biotechnological
approaches
construction
natural
unnatural
polysubstituted
4-hydroxy-2-pyrones.
The
major
synthetical
methods
biomimetic
based
cyclization
tricarbonyl
compounds.
Novel
de
novo
alkyne
cyclizations
using
metal
complexes
ketene
transformations
allow
straightforward
access
have
been
applied
Possible
directions
further
pyrone
ring
modification
discussed.
