Journal of Biological Chemistry,
Год журнала:
2023,
Номер
299(7), С. 104904 - 104904
Опубликована: Июнь 10, 2023
Nitrosuccinate
is
a
biosynthetic
building
block
in
many
microbial
pathways.
The
metabolite
produced
by
dedicated
L-aspartate
hydroxylases
that
use
NADPH
and
molecular
oxygen
as
co-substrates.
Here,
we
investigate
the
mechanism
underlying
unusual
ability
of
these
enzymes
to
perform
successive
rounds
oxidative
modifications.
crystal
structure
Streptomyces
sp.
V2
N-hydroxylase
outlines
characteristic
helical
domain
wedged
between
two
dinucleotide-binding
domains.
Together
with
FAD,
cluster
conserved
arginine
residues
forms
catalytic
core
at
interface.
Aspartate
found
bind
an
entry
chamber
close
but
not
direct
contact
flavin.
It
recognized
extensive
H-bond
network
explains
enzyme's
strict
substrate-selectivity.
A
mutant
designed
create
steric
electrostatic
hindrance
substrate
binding
disables
hydroxylation
without
perturbing
oxidase
side-activity.
Critically,
distance
FAD
far
too
long
afford
N-hydroxylation
C4a-hydroperoxyflavin
intermediate,
whose
formation
confirmed
our
work.
We
conclude
enzyme
functions
through
catch-and-release
mechanism.
slides
into
center
only
when
hydroxylating
apparatus
formed.
then
re-captured
where
it
waits
for
next
round
hydroxylation.
By
iterating
steps,
minimizes
leakage
incompletely
oxygenated
products
ensures
reaction
carries
on
until
nitrosuccinate
This
unstable
product
can
be
engaged
or
undergoes
spontaneous
decarboxylation
produce
3-nitropropionate,
mycotoxin.
Natural Product Reports,
Год журнала:
2024,
Номер
41(4), С. 604 - 648
Опубликована: Янв. 1, 2024
Covering:
1997
to
2023The
shikimate
pathway
is
the
metabolic
process
responsible
for
biosynthesis
of
aromatic
amino
acids
phenylalanine,
tyrosine,
and
tryptophan.
Seven
steps
convert
phosphoenolpyruvate
(PEP)
erythrose
4-phosphate
(E4P)
into
ultimately
chorismate,
which
serves
as
branch
point
dedicated
acid
biosynthesis.
Bacteria,
fungi,
algae,
plants
(yet
not
animals)
biosynthesize
chorismate
exploit
its
intermediates
in
their
specialized
metabolism.
This
review
highlights
diversity
derived
from
along
seven
PEP
E4P
well
additional
sections
on
compounds
prephenate,
anthranilate
synonymous
aminoshikimate
pathway.
We
discuss
genomic
basis
biochemical
support
leading
shikimate-derived
antibiotics,
lipids,
pigments,
cofactors,
other
metabolites
across
tree
life.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
144(28), С. 12954 - 12960
Опубликована: Июнь 30, 2022
Nitrogen–nitrogen
bond-containing
functional
groups
are
rare,
but
they
found
in
a
considerably
wide
class
of
natural
products.
Recent
clarifications
the
biosynthetic
routes
for
such
shed
light
onto
overlooked
genes
distributed
across
bacterial
kingdom,
highlighting
presence
yet-to-be
identified
products
with
peculiar
groups.
Here,
genome-mining
approach
targeting
unique
hydrazine-forming
gene
led
to
discovery
actinopyridazinones
A
(1)
and
B
(2),
first
dihydropyridazinone
rings.
The
structure
actinopyridazinone
was
unambiguously
established
by
total
synthesis.
Biosynthetic
studies
unveiled
structural
diversity
hydrazines
derived
from
this
family
N–N
bond-forming
enzymes.
Angewandte Chemie International Edition,
Год журнала:
2022,
Номер
61(45)
Опубликована: Сен. 17, 2022
The
diazo
group
is
an
important
functional
that
can
confer
biological
activity
to
natural
products
owing
its
high
reactivity.
Recent
studies
have
revealed
groups
are
synthesized
from
amino
using
nitrous
acid
in
secondary
metabolites
of
actinomycetes.
However,
genome
database
analysis
indicated
there
still
many
group-biosynthesizing
enzymes
for
unknown
biosynthetic
pathways.
Here,
we
discovered
avenalumic
biosynthesis
gene
cluster
Streptomyces
sp.
RI-77
by
mining
involved
formation.
Through
heterologous
expression,
the
was
direct
(AVA)
via
3-aminoavenalumic
(3-AAA).
In
vitro
enzyme
assays
showed
AvaA6
and
AvaA7
catalyzed
diazotization
3-AAA
substitution
hydride
synthesize
AVA,
respectively.
This
study
unprecedented
pathway
removal
diazotization.
Nitrogen-Nitrogen
(N-N)
bond-containing
functional
groups
in
natural
products
and
synthetic
drugs
play
significant
roles
exerting
biological
activities.
The
mechanisms
of
N-N
bond
formation
organic
molecules
have
garnered
increasing
attention
over
the
decades.
Recent
advances
illuminated
various
enzymatic
nonenzymatic
strategies,
our
understanding
construction
is
rapidly
expanding.
A
group
didomain
proteins
with
zinc-binding
cupin/methionyl-tRNA
synthetase
(MetRS)-like
domains,
also
known
as
hydrazine
synthetases,
generates
amino
acid-based
hydrazines,
which
serve
key
biosynthetic
precursors
diverse
functionalities
such
hydrazone,
diazo,
triazene,
pyrazole,
pyridazinone
groups.
In
this
review,
we
summarize
current
knowledge
on
pathways
employing
unique
bond-forming
machinery.
Journal of the American Chemical Society,
Год журнала:
2022,
Номер
145(1), С. 58 - 69
Опубликована: Дек. 19, 2022
Although
microbial
genomes
harbor
an
abundance
of
biosynthetic
gene
clusters,
there
remain
substantial
technological
gaps
that
impair
the
direct
correlation
newly
discovered
clusters
and
their
corresponding
secondary
metabolite
products.
As
example
one
approach
designed
to
minimize
or
bridge
such
gaps,
we
employed
hierarchical
clustering
analysis
principal
component
(
