Angewandte Chemie,
Journal Year:
2023,
Volume and Issue:
135(52)
Published: Nov. 14, 2023
Abstract
Die
Diterpensynthase
AlTS
aus
Aspergillus
luchuensis
wurde
identifiziert.
katalysiert
die
Bildung
des
Diterpenkohlenwasserstoffs
Spiroluchuen
A,
der
ein
neuartiges
Gerüst
aufweist,
das
durch
spirocyclisches
Ringsystem
gekennzeichnet
ist.
Der
Cyclisierungsmechanismus
zu
dieser
Verbindung
Isotopenmarkierungsexperimente
in
mit
DFT‐Berechnungen
und
metadynamischen
Simulationen
aufgeklärt.
Das
biosynthetische
Zwischenprodukt
Luchudien
neben
dem
Derivat
B
einer
Enzymvariante
abgefangen,
ortsspezifische
Mutagenese
erhalten
wurde.
Mit
seinem
10‐gliedrigen
Ring
ist
strukturell
Germacrenen
verwandt
kann
eine
Cope‐Umlagerung
Luchuelemen
eingehen.
ACS Catalysis,
Journal Year:
2023,
Volume and Issue:
13(19), P. 12774 - 12802
Published: Sept. 15, 2023
The
review
by
Christianson,
published
in
2017
on
the
twentieth
anniversary
of
emergence
field,
summarizes
foundational
discoveries
and
key
advances
terpene
synthase/cyclase
(TS)
biocatalysis
(Christianson,
D.
W.
PLoS ONE,
Journal Year:
2025,
Volume and Issue:
20(1), P. e0316606 - e0316606
Published: Jan. 31, 2025
The
exploration
of
potential
candidates
for
fungicides
against
four
fungal
proteins
that
cause
some
vital
plant
diseases,
namely
Phytophthora
capsici,
Botrytis
cinerea,
Fusarium
oxysporum
f.
sp.
lycopersici,
and
Puccinia
graminis
tritici,
was
conducted
using
in
silico,
molecular
docking
simulations,
dynamic
(MD)
simulation
selecting
the
nature
binding
affinity
with
actives
sites
proteins.
First
all,
DFT
employed
to
optimize
geometry,
get
prepared
optimized
ligand.
From
data,
chemical
descriptors
were
calculated.
Next,
two
tools,
such
as
AutoDock
by
PyRx
Molecular
Docking
Glide
from
Schrödinger
suite,
used
convey
score,
ligand
protein
interactions
main
proteases,
instance
7VEM,
8H6Q,
8EBB,
7XDS
having
name
pathogens:
respectively.
In
case
auto
dock
PyRx,
L01,
L03,
L04,
L13,
L14,
L17,
L18,
L19
demonstrated
significantly
higher
affinities
pathogens.
Surprisingly,
it
is
conveyed
L03
illustrated
highest
score
three
L09
8H6Q.
However,
MD
performed
check
validation
calculation
procedure
stability
docked
complex
accounting
RMSD,
RMSF,
SASA,
Radius
gyration
(Rg),
Protein
secondary
structure
elements
(SSE),
Ramachandran
plot
which
confirm
so
high,
number
calculating
hydrogen
bonds
more
than
good
enough,
a
result
concluded
valid.
Finally,
Difenoconazole
(L03)
has
been
considered
most
promising
antifungal
drug
evaluated
studies.
The Plant Journal,
Journal Year:
2025,
Volume and Issue:
121(6)
Published: March 1, 2025
SUMMARY
Ferns,
known
for
their
adaptability
and
widespread
presence,
form
a
diverse
group
of
plants.
However,
the
mechanisms
underlying
terpenoid
production,
which
are
often
linked
to
plant
adaptation,
not
well
understood
in
ferns.
Here,
we
report
that
Dryopteris
fragrans
(
D.
fragans
)
produces
terpenoids
glandular
trichomes
(GTs)
through
activities
microbial‐type
terpene
synthases.
Using
microscopy
methods,
capitate
GTs
were
found
occur
on
various
organs
throughout
development
.
In
leaves,
13
terpenoids,
most
being
sesquiterpenoids,
identified.
By
comparing
chemistry
intact
GT‐removed
isolated
GTs,
concluded
be
main
site
storage.
Next,
transcriptomes
leaves
created
mined
genes
biosynthetic
pathway.
Among
them
nine
putative
full‐length
microbial
synthase‐like
MTPSL
designated
DfMTPSL1–9
vitro
enzyme
assays,
six
DfMTPSLs
demonstrated
have
sesquiterpene
synthase
activities.
Of
them,
DfMTPSL1
catalyzes
formation
(−)‐9‐
epi
‐presilphiperfolan‐1‐ol,
abundant
sesquiterpenoid
leaves.
DfMTPS2
α‐muurolene,
another
major
from
The
catalytic
together
with
GT‐enriched
expression
respective
support
also
biosynthesis
Methyl
jasmonate
treatment
induced
DfMTPSL
emission
volatiles,
suggesting
GT‐produced
play
role
defense
against
biotic
stresses
,
similar
counterparts
seed
Journal of Agricultural and Food Chemistry,
Journal Year:
2024,
Volume and Issue:
72(13), P. 6871 - 6888
Published: March 25, 2024
Sesquiterpenes
comprise
a
diverse
group
of
natural
products
with
wide
range
applications
in
cosmetics,
food,
medicine,
agriculture,
and
biofuels.
Heterologous
biosynthesis
is
increasingly
employed
for
sesquiterpene
production,
aiming
to
overcome
the
limitations
associated
chemical
synthesis
extraction.
Sesquiterpene
synthases
(STSs)
play
crucial
role
heterologous
sesquiterpene.
Under
catalysis
STSs,
over
300
skeletons
are
produced
through
various
cyclization
processes
(C1-C10
closure,
C1-C11
C1-C6
C1-C7
closure),
which
responsible
diversity
sesquiterpenes.
According
types,
we
gave
an
overview
advances
understanding
mechanism
STSs
from
aspects
protein
crystal
structures
site-directed
mutagenesis.
We
also
summarized
engineering
Finally,
bottlenecks
potential
research
directions
related
application
modified
were
presented.
Angewandte Chemie International Edition,
Journal Year:
2024,
Volume and Issue:
63(23)
Published: April 8, 2024
Abstract
Little
is
known
about
the
structures
and
catalytic
mechanisms
of
sesterterpene
synthases
(StTSs),
which
greatly
hinders
structure‐based
engineering
StTSs
for
structural
diversity
expansion
sesterterpenes.
We
here
report
on
crystal
terpene
cyclization
(TC)
domains
two
fungal
StTSs:
sesterfisherol
synthase
(NfSS)
sesterbrasiliatriene
(PbSS).
Both
TC
contain
benzyltriethylammonium
chloride
(BTAC),
pyrophosphate
(PPi),
magnesium
ions
(Mg
2+
),
clearly
defining
active
sites.
A
combination
theory
experiments
including
carbocationic
intermediates
modeling,
site‐directed
mutagenesis,
isotope
labeling
provided
detailed
insights
into
basis
their
mechanisms.
Structure‐based
NfSS
PbSS
resulted
in
formation
20
sesterterpenes
13
new
compounds
four
pairs
epimers
with
different
configurations
at
C18.
These
results
expand
provide
important
future
synthetic
biology
research.
Angewandte Chemie International Edition,
Journal Year:
2023,
Volume and Issue:
62(52)
Published: Nov. 14, 2023
The
diterpene
synthase
AlTS
was
identified
from
Aspergillus
luchuensis.
catalyses
the
formation
of
hydrocarbon
spiroluchuene
A,
which
exhibits
a
novel
skeleton
characterised
by
spirocyclic
ring
system.
cyclisation
mechanism
towards
this
compound
elucidated
through
isotopic
labelling
experiments
in
conjunction
with
DFT
calculations
and
metadynamic
simulations.
biosynthetic
intermediate
luchudiene,
besides
derivative
B,
captured
an
enzyme
variant
obtained
site-directed
mutagenesis.
With
its
10-membered
luchudiene
is
structurally
related
to
germacrenes
can
undergo
Cope
rearrangement
luchuelemene.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(26), P. 17838 - 17846
Published: June 18, 2024
Presilphiperfolan-8β-ol
synthase
(BcBOT2),
a
substrate-promiscuous
sesquiterpene
cyclase
(STC)
of
fungal
origin,
is
capable
converting
two
new
farnesyl
pyrophosphate
(FPP)
derivatives
modified
at
C7
bearing
either
hydroxymethyl
group
or
methoxymethyl
group.
These
substrates
were
chosen
based
on
computationally
generated
model.
Biotransformations
yielded
five
oxygenated
terpenoids.
Remarkably,
the
formation
one
these
tricyclic
products
can
only
be
explained
by
cationically
induced
migration
methoxy
group,
presumably
via
Meerwein-salt
intermediate,
unprecedented
in
synthetic
chemistry
and
biosynthesis.
The
results
show
great
principle
general
potential
terpene
cyclases
for
mechanistic
studies
unusual
cation
creation
skeletons.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
unknown, P. 17699 - 17715
Published: Nov. 15, 2024
Enzymes'
catalytic
promiscuity
enables
the
alteration
of
product
specificity
via
protein
engineering;
yet,
harnessing
this
to
achieve
desired
reactions
remains
challenging.
Here,
we
identified
HCinS,
a
monoterpene
synthase
(MTPS)
with
high
efficiency
and
for
1,8-cineole
biosynthesis.
Quantum
mechanics/molecular
mechanics
(QM/MM)
simulations,
which
were
performed
based
on
resolved
crystal
structure
revealed
mechanistic
details
biosynthetic
cascade
reactions.
Guided
by
these
insights,
in
silico
HCinS
variants
designed
fine-tuned
transition-state
energies
reaction
microenvironments.
Three
(T111A,
N135H,
F236M),
each
one
amino
acid
substitution,
exhibited
production
monocyclic
(R)-α-terpineol,
(R)-limonene,
acyclic
myrcene,
respectively,
maintaining
over
55%
native
HCinS.
These
surpassed
naturally
evolved
isozymes
capacity
enabled
yeast
highest
microbial
titer
corresponding
terpene.
Furthermore,
single
mutation
four
functional
equivalent
acids
other
TPSs,
resulted
expected
shifts
as
variants.
This
research
offers
insights
into
mechanisms
controlling
TPS's
highlights
universal
applicability
computational
design
reshaping
thereby
paving
innovative
avenues
creating
enzymes
applications
chemistry
synthetic
biology.
ACS Catalysis,
Journal Year:
2024,
Volume and Issue:
14(10), P. 7389 - 7401
Published: April 27, 2024
PtlD,
a
multifunctional
mononuclear
nonheme
iron
and
α-ketoglutarate-dependent
(NHFe/α-KG)
dioxygenase
involved
in
neopentalenoketolactone
biosynthesis,
catalyzes
hydroxylation,
desaturation,
olefin
epoxidation
reactions.
Investigating
desaturation
reactions
of
nonactivated
carbons
mediated
by
NHFe/α-KG
enzymes
is
intriguing,
especially
for
understanding
the
fate
substrate
radicals
formed
after
hydrogen
atom
abstraction
FeIV═O
species.
Here,
we
investigate
reaction
mechanism
PtlD
using
two
distinct
substrates:
neopentalenolactone
D
(1)
features
lone
pair-containing
oxygen
adjacent
to
olefin-forming
carbon
atoms,
whereas
pentalenolactone
(7)
harbors
carbonyl
group
at
corresponding
position.
For
1,
our
isotope
effect
measurement
protein
mutagenesis
experiments
suggest
formation
carbocation
intermediate,
which
subsequently
deprotonated
base
generate
products.
Residue
K288
serves
as
base,
while
Y113
likely
stabilizes
via
π-cation
interaction.
7,
incorporation
patterns
indicated
that
intermediate
also
but
unstable,
leading
hydroxylation
due
H2O
quenching.
Notably,
7's
exhibits
temperature-dependent
large
kinetic
(KIE)
an
inverse
solvent
(SIE),
suggesting
tunneling
contributes
electron–proton
transfer
(EPT)
process.
These
findings
collectively
reveal
cases
enzymes,
where
mechanisms
switch
with
different
substrates.