Catalysis Today,
Journal Year:
2024,
Volume and Issue:
442, P. 114925 - 114925
Published: July 9, 2024
Hydrolases
are
well-known
for
hydrolyzing
esters,
amides,
carbamates,
peptides,
or
acid
anhydrides
in
the
presence
of
water.
However,
some
them
also
capable
catalyzing
reverse
reaction
(condensation)
under
certain
conditions
aqueous
systems.
Hence,
these
enzymes
called
promiscuous
hydrolases/acyltransferases.
This
review
deals
with
their
discovery,
background
information
on
mechanism
action,
and
significant
improvements
by
enzyme
engineering
to
both
enhance
product
formation
decrease
undesired
hydrolysis
targeted
acyl
products.
Their
applications
biocatalysis
exemplified
synthesis
a
wide
range
esters
amides
systems,
including
preparative-scale
processes
combination
hydrolases/acyltransferases
other
cascade
reactions
utilize
alternative
feedstocks
from
renewable
resources,
example.
Complementary,
use
ATP-dependent
amide
synthesizing
is
covered.
Together,
represent
practically
useful
alternatives
well-established
chemical
reactions,
operating
solutions
that
appeal
different
industries.
Cell,
Journal Year:
2024,
Volume and Issue:
187(11), P. 2717 - 2734.e33
Published: April 22, 2024
The
gut
microbiota
has
been
found
to
play
an
important
role
in
the
progression
of
metabolic
dysfunction-associated
steatohepatitis
(MASH),
but
mechanisms
have
not
established.
Here,
by
developing
a
click-chemistry-based
enrichment
strategy,
we
identified
several
microbial-derived
bile
acids,
including
previously
uncharacterized
3-succinylated
cholic
acid
(3-sucCA),
which
is
negatively
correlated
with
liver
damage
patients
liver-tissue-biopsy-proven
fatty
disease
(MAFLD).
By
screening
human
bacterial
isolates,
Bacteroides
uniformis
strains
as
effective
producers
3-sucCA
both
vitro
and
vivo.
activity-based
protein
purification
identification,
enzyme
annotated
β-lactamase
B.
responsible
for
biosynthesis.
Furthermore,
that
lumen-restricted
metabolite
alleviates
MASH
promoting
growth
Akkermansia
muciniphila.
Together,
our
data
offer
new
insights
into
microbiota-liver
axis
may
be
leveraged
augment
management
MASH.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: April 25, 2024
Bile
acids,
once
considered
mere
dietary
surfactants,
now
emerge
as
critical
modulators
of
macronutrient
(lipid,
carbohydrate,
protein)
metabolism
and
the
systemic
pro-inflammatory/anti-inflammatory
balance.
acid
signaling
pathways
play
a
crucial
role
in
protecting
against,
or
if
aberrant,
inducing
cardiometabolic,
inflammatory,
neoplastic
conditions,
strongly
influencing
health
disease.
No
curative
treatment
exists
for
any
bile
influenced
disease,
while
most
promising
well-developed
therapeutic
was
recently
rejected
by
FDA.
Here,
we
provide
bottom-up
approach
on
mechanistically
explaining
their
biochemistry,
physiology,
pharmacology
at
canonical
non-canonical
receptors.
Using
this
mechanistic
model
explain
how
abnormal
physiology
drives
disease
pathogenesis,
emphasizing
ceramide
synthesis
may
serve
unifying
pathogenic
feature
cardiometabolic
diseases.
We
an
in-depth
summary
pre-existing
receptor
modulators,
shortcomings,
propose
solutions
they
be
remedied.
Lastly,
rationalize
novel
targets
further
translational
drug
discovery
future
perspectives.
Rather
than
dismissing
therapeutics
due
to
recent
setbacks,
believe
that
there
is
immense
clinical
potential
high
likelihood
success
therapeutics.
Cell,
Journal Year:
2024,
Volume and Issue:
187(7), P. 1801 - 1818.e20
Published: March 1, 2024
The
repertoire
of
modifications
to
bile
acids
and
related
steroidal
lipids
by
host
microbial
metabolism
remains
incompletely
characterized.
To
address
this
knowledge
gap,
we
created
a
reusable
resource
tandem
mass
spectrometry
(MS/MS)
spectra
filtering
1.2
billion
publicly
available
MS/MS
for
bile-acid-selective
ion
patterns.
Thousands
are
distributed
throughout
animal
human
bodies
as
well
cultures.
We
employed
library
identify
polyamine
amidates,
prevalent
in
carnivores.
They
present
humans,
their
levels
alter
with
diet
change
from
Mediterranean
typical
American
diet.
This
work
highlights
the
existence
many
more
acid
than
previously
recognized
value
leveraging
public
large-scale
untargeted
metabolomics
data
discover
metabolites.
availability
modification-centric
will
inform
future
studies
investigating
roles
health
disease.
Gut Microbes,
Journal Year:
2024,
Volume and Issue:
16(1)
Published: May 20, 2024
Inflammatory
bowel
disease
(IBD)
is
a
chronic
and
recurrent
condition
affecting
the
gastrointestinal
tract.
Disturbed
gut
microbiota
abnormal
bile
acid
(BA)
metabolism
are
notable
in
IBD,
suggesting
bidirectional
relationship.
Specifically,
diversity
of
influences
BA
composition,
whereas
altered
profiles
can
disrupt
microbiota.
IBD
patients
often
exhibit
increased
primary
reduced
secondary
concentrations
due
to
diminished
bacteria
population
essential
for
metabolism.
This
imbalance
activates
receptors,
undermining
intestinal
integrity
immune
function.
Consequently,
targeting
microbiota-BA
axis
may
rectify
these
disturbances,
offering
symptomatic
relief
IBD.
Here,
interplay
between
acids
(BAs)
reviewed,
with
particular
focus
on
role
mediating
biotransformation,
contributions
pathology
unveil
potential
novel
therapeutic
avenues
Gut Microbes,
Journal Year:
2025,
Volume and Issue:
17(1)
Published: Jan. 8, 2025
Alterations
in
bile
acid
profile
and
pathways
contribute
to
hepatic
inflammation
cancer
cachexia,
a
syndrome
worsening
the
prognosis
of
patients.
As
gut
microbiota
impinges
on
host
metabolism
through
acids,
current
study
aimed
explore
functional
contribution
microbial
dysbiosis
dysmetabolism
associated
disorders
cachexia.
Using
three
mouse
models
cachexia
(the
C26,
MC38
HCT116
models),
we
evidenced
reduction
levels
several
secondary
mainly
taurodeoxycholic
(TDCA).
This
TDCA
occurred
before
appearance
Longitudinal
analysis
pinpointed
an
ASV,
identified
as
Xylanibacter
rodentium,
bacterium
potentially
involved
reduced
production
TDCA.
Coherently,
stable
isotope-based
experiments
highlighted
robust
decrease
7α-dehydroxylation
(7α-DH)
activity
with
no
changes
salt
hydrolase
(BSH)
cachectic
mice.
approach
also
7α-hydroxysteroid
dehydrogenase
(7α-HSDH)
12α-hydroxysteroid
(12α-HSDH)
activities
these
The
lower
was
explored
vitro
vivo.
In
vitro,
prevented
myotube
atrophy,
whereas
vivo
whole
transcriptome
revealed
that
administration
mice
improved
unfolded
protein
response
cholesterol
homeostasis
pathways.
reversed
accumulation
Altogether,
this
work
highlights
therapeutic
interest
for
context
Such
discovery
may
prove
instrumental
understanding
other
metabolic
diseases
characterized
by
dysbiosis.
More
broadly,
our
demonstrates
relevance
measurements
using
isotopes,
currently
underused
microbiome
field.
