Angewandte Chemie International Edition,
Год журнала:
2021,
Номер
60(43), С. 23159 - 23163
Опубликована: Авг. 11, 2021
The
eunicellane
diterpenoids
are
a
unique
family
of
natural
products
seen
in
marine
organisms,
plants,
and
bacteria.
We
used
series
biochemical,
bioinformatics,
theoretical
experiments
to
investigate
the
mechanism
first
diterpene
synthase
known
form
skeleton.
Deuterium
labeling
studies
quantum
chemical
calculations
support
that
Bnd4,
from
Streptomyces
sp.
(CL12-4),
forms
6,10-bicyclic
skeleton
through
1,10-cyclization,
1,3-hydride
shift,
1,14-cyclization
cascade.
Bnd4
also
demonstrated
sesquiterpene
cyclase
activity
ability
prenylate
small
molecules.
possesses
D
Nucleic Acids Research,
Год журнала:
2021,
Номер
50(D1), С. D1317 - D1323
Опубликована: Окт. 4, 2021
Within
the
natural
products
field
there
is
an
increasing
emphasis
on
study
of
compounds
from
microbial
sources.
This
has
been
fuelled
by
interest
in
central
role
that
microorganisms
play
mediating
both
interspecies
interactions
and
host-microbe
relationships.
To
support
chemistry
produced
we
released
Natural
Products
Atlas,
a
database
known
structures,
2019.
paper
reports
release
new
version
which
includes
full
RESTful
application
programming
interface
(API),
website
framework,
expanded
8128
compounds,
bringing
total
to
32
552.
In
addition
these
structural
content
changes
have
added
taxonomic
descriptions
for
all
taxa
chemical
ontology
terms
NP
Classifier
ClassyFire.
We
also
performed
manual
curation
review
entries
with
incomplete
configurational
assignments
integrated
data
external
resources,
including
CyanoMetDB.
Finally,
improved
user
experience
updating
Overview
dashboard
creating
origin.
The
can
be
accessed
via
interactive
at
https://www.npatlas.org.
Journal of the American Chemical Society,
Год журнала:
2023,
Номер
145(15), С. 8474 - 8485
Опубликована: Апрель 5, 2023
The
cyclization
of
farnesyl
diphosphate
(FPP)
into
highly
strained
polycyclic
sesquiterpenes
is
challenging.
We
here
determined
the
crystal
structures
three
sesquiterpene
synthases
(STSs,
namely,
BcBOT2,
DbPROS,
and
CLM1)
catalyzing
biosynthesis
tricyclic
presilphiperfolan-8β-ol
(1),
Δ6-protoilludene
(2),
longiborneol
(3).
All
STS
contain
a
substrate
mimic,
benzyltriethylammonium
cation
(BTAC),
in
their
active
sites,
providing
ideal
templates
for
quantum
mechanics/molecular
mechanics
(QM/MM)
analyses
toward
catalytic
mechanisms.
QM/MM-based
molecular
dynamics
(MD)
simulations
revealed
cascade
reactions
enzyme
products,
different
key
site
residues
that
play
important
roles
stabilizing
reactive
carbocation
intermediates
along
pathways.
Site-directed
mutagenesis
experiments
confirmed
these
concomitantly
resulted
17
shunt
products
(4-20).
Isotopic
labeling
addressed
hydride
methyl
migrations
main
several
products.
These
combined
methods
provided
deep
insights
mechanisms
STSs
demonstrated
how
chemical
space
can
rationally
be
expanded,
which
may
facilitate
applications
synthetic
biology
approaches
pharmaceutical
perfumery
agents.
Natural Product Reports,
Год журнала:
2024,
Номер
41(5), С. 748 - 783
Опубликована: Янв. 1, 2024
This
review
covers
all
fungal
terpenoid
cyclases
(TCs),
including
class
I
and
II
TCs
as
well
emerging
UbiA-type
TCs,
together
with
their
tailoring
enzymes,
focusing
on
newly
identified
enzymes
from
2015
to
August
2023.
Natural Product Reports,
Год журнала:
2021,
Номер
39(2), С. 249 - 272
Опубликована: Окт. 9, 2021
Terpenoids
have
diverse
bioecological
roles
in
all
kingdoms
of
life.
Here
we
discuss
the
evolution
and
ecological
functions
microbial
terpenoids
their
possible
applications.
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(9)
Опубликована: Фев. 21, 2023
Sea
sponges
are
the
largest
marine
source
of
small-molecule
natural
products
described
to
date.
Sponge-derived
molecules,
such
as
chemotherapeutic
eribulin,
calcium-channel
blocker
manoalide,
and
antimalarial
compound
kalihinol
A,
renowned
for
their
impressive
medicinal,
chemical,
biological
properties.
Sponges
contain
microbiomes
that
control
production
many
isolated
from
these
invertebrates.
In
fact,
all
genomic
studies
date
investigating
metabolic
origins
sponge-derived
small
molecules
concluded
microbes—not
sponge
animal
host—are
biosynthetic
producers.
However,
early
cell-sorting
suggested
host
may
play
a
role
particularly
in
terpenoid
molecules.
To
investigate
genetic
underpinnings
biosynthesis,
we
sequenced
metagenome
transcriptome
an
isonitrile
sesquiterpenoid-containing
order
Bubarida.
Using
bioinformatic
searches
biochemical
validation,
identified
group
type
I
terpene
synthases
(TSs)
this
multiple
other
species,
first
enzyme
class
characterized
holobiome.
The
Bubarida
TS-associated
contigs
consist
intron-containing
genes
homologous
feature
GC
percentage
coverage
consistent
with
eukaryotic
sequences.
We
TS
homologs
five
different
species
geographically
distant
locations,
thereby
suggesting
broad
distribution
amongst
sponges.
This
work
sheds
light
on
secondary
metabolite
speaks
possibility
sponge-specific
originate
host.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Июль 6, 2023
Abstract
Diterpene
synthase
VenA
is
responsible
for
assembling
venezuelaene
A
with
a
unique
5-5-6-7
tetracyclic
skeleton
from
geranylgeranyl
pyrophosphate.
also
demonstrates
substrate
promiscuity
by
accepting
geranyl
pyrophosphate
and
farnesyl
as
alternative
substrates.
Herein,
we
report
the
crystal
structures
of
in
both
apo
form
holo
complex
trinuclear
magnesium
cluster
group.
Functional
structural
investigations
on
atypical
115
DSFVSD
120
motif
VenA,
versus
canonical
Asp-rich
DDXX(X)D/E,
reveal
that
absent
second
Asp
functionally
replaced
Ser116
Gln83,
together
bioinformatics
analysis
identifying
hidden
subclass
type
I
microbial
terpene
synthases.
Further
analysis,
multiscale
computational
simulations,
structure-directed
mutagenesis
provide
significant
mechanistic
insights
into
selectivity
catalytic
VenA.
Finally,
semi-rationally
engineered
sesterterpene
to
recognize
larger
geranylfarnesyl
