bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 13, 2024
Abstract
Monoterpene
indole
alkaloids
(MIAs)
are
a
large,
structurally
diverse
class
of
bioactive
natural
products.
These
compounds
biosynthetically
derived
from
stereoselective
Pictet-Spengler
condensation
that
generates
tetrahydro-β-carboline
scaffold
characterized
by
3
S
stereocenter.
However,
subset
MIAs
contain
non-canonical
R
Herein,
we
report
the
basis
for
-MIA
biosynthesis
in
Mitragyna
speciosa
(Kratom).
We
discover
presence
iminium
species,
20
-3-dehydrocorynantheidine,
which
led
us
to
hypothesize
isomerization
occurs
oxidation
and
reduction
downstream
initial
condensation.
Isotopologue
feeding
experiments
implicated
young
leaves
stems
as
sites
pathway
biosynthesis,
facilitating
identification
an
oxidase/reductase
pair
catalyzes
this
epimerization.
This
enzyme
has
broad
substrate
specificity,
suggesting
oxidase
reductase
may
be
responsible
formation
many
-MIAs
spirooxindole
Kratom.
enzymes
allow
biocatalytic
access
range
previously
inaccessible
pharmacologically
active
compounds.
Journal of the American Chemical Society,
Journal Year:
2023,
Volume and Issue:
145(9), P. 4957 - 4963
Published: Feb. 22, 2023
Mitragyna
speciosa
("kratom")
is
used
as
a
natural
remedy
for
pain
and
management
of
opioid
dependence.
The
pharmacological
properties
kratom
have
been
linked
to
complex
mixture
monoterpene
indole
alkaloids,
most
notably
mitragynine.
Here,
we
report
the
central
biosynthetic
steps
responsible
scaffold
formation
mitragynine
related
corynanthe-type
alkaloids.
We
illuminate
mechanistic
basis
by
which
key
stereogenic
center
this
formed.
These
discoveries
were
leveraged
enzymatic
production
mitragynine,
C-20
epimer
speciogynine,
fluorinated
analogues.
ACS Chemical Biology,
Journal Year:
2023,
Volume and Issue:
18(8), P. 1772 - 1785
Published: July 31, 2023
The
detailed
metabolic
map
for
camptothecin
(CPT)
biosynthesis
in
Camptotheca
acuminata
has
been
proposed
according
to
our
combined
omics
results.
However,
the
CYP450-mediated
epoxidation
step
CPT
remains
unexplored.
A
proteomics-guided
approach
was
used
identify
and
annotate
proteins
enriched
during
vigorous
metabolism
period
mature
C.
seedlings.
Comparative
analyses
revealed
that
flavonoid
biosyntheses
were
stems
all
of
samples
except
leaves,
respectively.
CYP71BE
genes
screened
based
on
their
enrichment
patterns
at
transcriptomic-proteomic
level
biochemically
characterized
Saccharomyces
cerevisiae
WAT11.
Four
exhibited
vitro
isoliquiritigenin
epoxidase
activity.
Additionally,
CYP71BE206
showed
activity
toward
strictosamide,
critical
precursor
biosynthesis,
both
Nicotiana
benthamiana.
In
planta
functional
verification
suggested
is
involved
biosynthesis.
Their
catalytic
conditions
optimized,
enzymatic
parameters
determined.
This
study
provides
valuable
insight
into
CYP71BE-mediated
offers
evidence
verify
newly
(CYP71BE206)
simultaneously
responsible
this
plant.
An
evolution
event
probably
happened
ancestral
CYP71BE,
resulting
neofunctionalization
CYP71BE206.
Current Opinion in Biotechnology,
Journal Year:
2024,
Volume and Issue:
87, P. 103135 - 103135
Published: May 9, 2024
Plant
bioactives
hold
immense
potential
in
the
medicine
and
food
industry.
The
recent
advancements
omics
applied
deciphering
specialized
metabolic
pathways
underscore
importance
of
high-quality
genome
releases
wealth
data
metabolomics
transcriptomics.
While
harnessing
data,
whether
integrated
or
standalone,
has
proven
successful
unveiling
plant
natural
product
(PNP)
biosynthetic
pathways,
democratization
machine
learning
biology
opens
exciting
new
opportunities
for
enhancing
exploration
these
pathways.
This
review
highlights
breakthroughs
disrupting
plant-specialized
through
utilization
techniques.
Genome,
Journal Year:
2025,
Volume and Issue:
68, P. 1 - 23
Published: Jan. 1, 2025
Canada
has
made
significant
contributions
to
the
field
of
plant
biochemistry,
with
numerous
researchers
actively
focusing
on
elucidating
biosynthetic
pathways
specialized
metabolites
and
producing
these
compounds
in
heterologous
systems,
such
as
bacteria,
yeast,
or
other
species.
The
review
aims
highlight
strengths
Canadian
research
this
domain
over
last
three
decades.
It
will
describe
advances
pathway
elucidation,
enzyme
characterization,
production
enzymes
particularly
areas
alkaloids,
terpenoids,
phenolic
compounds.
have
not
only
pivotal
scientific
discoveries
but
also
ensured
continuity
excellence
by
mentoring
new
generations
principal
investigators
metabolites.
These
warrant
recognition
financial
support
retain
future
talent
maintain
Canada's
leadership
progress
global
stage.
Plants,
Journal Year:
2024,
Volume and Issue:
13(7), P. 966 - 966
Published: March 27, 2024
Hamelia
patens
(Rubiaceae),
known
as
firebush,
is
a
source
of
bioactive
monoterpenoid
oxindole
alkaloids
(MOAs)
derived
from
indole
(MIAs).
With
the
aim
understanding
regulation
biosynthesis
these
specialized
metabolites,
micropropagated
plants
were
elicited
with
jasmonic
acid
(JA)
and
salicylic
(SA).
The
MOA
production
MIA
biosynthetic-related
gene
expression
evaluated
over
time.
MOAs
was
increased
compared
to
control
up
2-fold
(41.3
mg
g
DW−1)
at
72
h
in
JA-elicited
2.5-fold
(42.4
120
SA.
increment
concurs
increase
levels
genes
HpaLAMT,
HpaTDC,
HpaSTR,
HpaNPF2.9,
HpaTHAS1,
HpaTHAS2.
Interestingly,
it
found
that
HpaSGD
downregulated
both
treatments
after
24
but
SA
treatment
only
upregulated
8-fold
control.
In
this
work,
we
present
results
H.
discuss
how
JA
might
be
regulating
central
biosynthetic
steps
involve
HpaTHAS
genes.
