Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(48), С. 22067 - 22074
Опубликована: Ноя. 23, 2022
Terpene
cyclases
(TCs),
extraordinary
enzymes
that
create
the
structural
diversity
seen
in
terpene
natural
products,
are
traditionally
divided
into
two
classes,
class
I
and
II.
Although
mechanistic
features
of
TCs
well-known,
corresponding
details
II
counterparts
have
not
been
fully
characterized.
Here,
we
report
genome
mining
discovery
characterization
sesquiterpene
(STCs)
from
Streptomyces.
These
drimenyl
diphosphate
synthases
(DMSs)
first
STCs
shown
to
possess
β,γ-didomain
architecture.
High-resolution
X-ray
crystal
structures
DMS
Streptomyces
showdoensis
(SsDMS)
complex
with
both
a
farnesyl
Mg2+
unveiled
an
induced-fit
mechanism,
unprecedented
binding
mode,
finally
solving
one
lingering
questions
TC
enzymology.
This
study
supports
continued
for
novel
bacterial
provides
new
insights
canonical
will
lead
advances
engineering
synthetic
biology.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(13), С. 11184 - 11184
Опубликована: Июль 6, 2023
Filamentous
fungi
are
one
of
the
most
important
producers
secondary
metabolites.
Some
them
can
have
a
toxic
effect
on
human
body,
leading
to
diseases.
On
other
hand,
they
widely
used
as
pharmaceutically
significant
drugs,
such
antibiotics,
statins,
and
immunosuppressants.
A
single
fungus
species
in
response
various
signals
produce
100
or
more
Such
signaling
is
possible
due
coordinated
regulation
several
dozen
biosynthetic
gene
clusters
(BGCs),
which
mosaically
localized
different
regions
fungal
chromosomes.
Their
includes
levels,
from
pathway-specific
regulators,
whose
genes
inside
BGCs,
global
regulators
cell
(taking
into
account
changes
pH,
carbon
consumption,
etc.)
metabolism
(affecting
epigenetic
driven
by
velvet
family
proteins,
LaeA,
etc.).
In
addition,
low-molecular-weight
substances
mediating
regulatory
processes.
This
review
devoted
critical
analysis
available
data
"turning
on"
"off"
biosynthesis
metabolites
filamentous
fungi.
To
describe
ongoing
processes,
model
"piano
regulation"
proposed,
whereby
pressing
certain
key
(signal)
leads
extraction
sound
"musical
instrument
cell",
expressed
production
specific
metabolite.
Chemical Science,
Год журнала:
2023,
Номер
14(13), С. 3661 - 3667
Опубликована: Янв. 1, 2023
Terpenoids
comprise
the
most
chemically
and
structurally
diverse
family
of
natural
products.
In
contrast
to
huge
numbers
terpenoids
discovered
from
plants
fungi,
only
a
relatively
small
number
were
reported
bacteria.
Recent
genomic
data
in
bacteria
suggest
that
large
biosynthetic
gene
clusters
encoding
remain
uncharacterized.
order
enable
functional
characterization
terpene
synthase
relevant
tailoring
enzymes,
we
selected
optimized
an
expression
system
based
on
Streptomyces
chassis.
Through
genome
mining,
16
distinct
bacterial
13
them
successfully
expressed
chassis,
leading
11
skeletons
including
three
new
ones,
representing
∼80%
success
rate.
addition,
after
genes,
18
novel
isolated
characterized.
This
work
demonstrates
advantages
chassis
which
not
enabled
successful
production
synthases,
but
also
especially
P450,
for
terpenoid
modification.
Angewandte Chemie International Edition,
Год журнала:
2020,
Номер
59(52), С. 23772 - 23781
Опубликована: Сен. 18, 2020
Fungal
meroterpenoids
are
a
diverse
group
of
hybrid
natural
products
with
impressive
structural
complexity
and
high
potential
as
drug
candidates.
In
this
work,
we
evaluate
the
promiscuity
early
structure
diversity-generating
step
in
fungal
meroterpenoid
biosynthetic
pathways:
multibond-forming
polyene
cyclizations
catalyzed
by
yet
poorly
understood
family
cyclases.
total,
12
unnatural
were
accessed
chemoenzymatically
using
synthetic
substrates.
Their
complex
structures
determined
2D
NMR
studies
well
crystalline-sponge-based
X-ray
diffraction
analyses.
The
results
obtained
revealed
degree
enzyme
experimental
which
together
quantum
chemical
calculations
provided
deeper
insight
into
catalytic
activity
new
non-canonical,
terpene
knowledge
paves
way
to
design
engineer
artificial
pathways
towards
second
generation
valuable
bioactivities
based
on
combinatorial
strategies.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(48), С. 22067 - 22074
Опубликована: Ноя. 23, 2022
Terpene
cyclases
(TCs),
extraordinary
enzymes
that
create
the
structural
diversity
seen
in
terpene
natural
products,
are
traditionally
divided
into
two
classes,
class
I
and
II.
Although
mechanistic
features
of
TCs
well-known,
corresponding
details
II
counterparts
have
not
been
fully
characterized.
Here,
we
report
genome
mining
discovery
characterization
sesquiterpene
(STCs)
from
Streptomyces.
These
drimenyl
diphosphate
synthases
(DMSs)
first
STCs
shown
to
possess
β,γ-didomain
architecture.
High-resolution
X-ray
crystal
structures
DMS
Streptomyces
showdoensis
(SsDMS)
complex
with
both
a
farnesyl
Mg2+
unveiled
an
induced-fit
mechanism,
unprecedented
binding
mode,
finally
solving
one
lingering
questions
TC
enzymology.
This
study
supports
continued
for
novel
bacterial
provides
new
insights
canonical
will
lead
advances
engineering
synthetic
biology.
