Learning from Protein Engineering by Deconvolution of Multi‐Mutational Variants
Angewandte Chemie International Edition,
Год журнала:
2024,
Номер
63(36)
Опубликована: Июнь 17, 2024
Abstract
This
review
analyzes
a
development
in
biochemistry,
enzymology
and
biotechnology
that
originally
came
as
surprise.
Following
the
establishment
of
directed
evolution
stereoselective
enzymes
organic
chemistry,
concept
partial
or
complete
deconvolution
selective
multi‐mutational
variants
was
introduced.
Early
experiments
led
to
finding
mutations
can
interact
cooperatively
antagonistically
with
one
another,
not
just
additively.
During
past
decade,
this
phenomenon
shown
be
general.
In
some
studies,
molecular
dynamics
(MD)
quantum
mechanics/molecular
mechanics
(QM/MM)
computations
were
performed
order
shed
light
on
origin
non‐additivity
at
all
stages
an
evolutionary
upward
climb.
Data
used
construct
unique
multi‐dimensional
rugged
fitness
pathway
landscapes,
which
provide
mechanistic
insights
different
from
traditional
landscapes.
Along
related
line,
biochemists
have
long
tested
result
introducing
two
point
enzyme
for
reasons,
followed
by
comparison
respective
double
mutant
so‐called
cycles,
showed
only
additive
effects,
but
more
recently
also
uncovered
cooperative
antagonistic
non‐additive
effects.
We
conclude
suggestions
future
work,
call
unified
overall
picture
epistasis.
Язык: Английский
Interactions of non-starch polysaccharides with the gut microbiota and the effect of non-starch polysaccharides with different structures on the metabolism of the gut microbiota: A review
International Journal of Biological Macromolecules,
Год журнала:
2025,
Номер
296, С. 139664 - 139664
Опубликована: Янв. 9, 2025
Язык: Английский
Salidroside production through cascade biocatalysis with a thermostability-enhanced UDP-glycosyltransferase
International Journal of Biological Macromolecules,
Год журнала:
2025,
Номер
299, С. 140261 - 140261
Опубликована: Янв. 23, 2025
Язык: Английский
Salidroside: Diverse Synthetic Pathways and Recent Advances in Pharmacological Effects Across Multiple Systems
Pharmacological Research - Natural Products,
Год журнала:
2025,
Номер
unknown, С. 100176 - 100176
Опубликована: Фев. 1, 2025
Язык: Английский
Engineering of Glycosyltransferase for Efficient Biosynthesis of Salidroside
Journal of Agricultural and Food Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 28, 2025
Salidroside
has
been
widely
used
in
the
cosmetic
and
medicinal
industries.
Previously,
potential
glycosyltransferase
UGTBS
was
obtained
for
salidroside
synthesis.
However,
catalytic
efficiency
undesirable.
In
this
study,
a
semirational
design
applied
to
engineer
UGTBS.
The
quadruple
mutant
M4
(I62N/S129T/F168W/Y316S)
showed
significantly
enhanced
A
conversion
rate
of
94.7%
using
M4,
which
2.2-fold
higher
than
that
wild-type.
regioselectivity
toward
tyrosol
hydroxyl
also
improved,
resulting
97.9%
total
product,
1.2-fold
wild
type.
Kinetic
constants
molecular
simulations
indicated
increased
affinity
altered
conformation
binding
pocket
accounted
Furthermore,
fed-batch
cascade
reaction
strategy
used,
over
183
mM
obtained.
engineered
demonstrated
precise
catalysis
formation.
Язык: Английский
Engineering Escherichia coli for Efficient De Novo Synthesis of Salidroside
Journal of Agricultural and Food Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 12, 2024
Salidroside
is
a
high-value
plant-derived
glycoside
with
diverse
biological
activities,
but
the
main
industrial
salidroside
production
method,
extraction
from
Язык: Английский
Lernen aus Protein‐Engineering durch Dekonvolution von Multi‐Mutationalen Enzymvarianten**
Angewandte Chemie,
Год журнала:
2024,
Номер
136(36)
Опубликована: Июнь 17, 2024
Abstract
Diese
Übersicht
analysiert
eine
Entwicklung
in
der
Biochemie,
Enzymologie
und
Biotechnologie,
die
ursprünglich
als
Überraschung
betrachtet
wurde.
Nach
Etablierung
gerichteten
Evolution
stereoselektiver
Enzyme
organischen
Chemie
wurde
das
Konzept
partiellen
oder
vollständigen
Dekonvolution
selektiver
multi‐mutationaler
Varianten
eingeführt.
Frühe
Dekonvolutionsexperimente
von
stereoselektiven
Enzymvarianten
führten
zu
Erkenntnis,
dass
Mutationen
kooperativ
antagonistisch
miteinander
interagieren
können,
nicht
nur
additiv.
Im
letzten
Jahrzehnt
dieses
Phänomen
allgemeingültig
nachgewiesen.
In
einigen
Studien
wurden
molekulardynamische
(MD)
quantenmechanische/
molekülmechanische
(QM/MM)
Berechnungen
durchgeführt,
um
Licht
auf
den
Ursprung
Nicht‐Additivität
allen
Phasen
eines
evolutionären
Aufstiegs
werfen.
Daten
können
verwendet
werden,
einzigartige
mehrdimensionale,
zerklüftete
(„rugged“)
Fitness‐Pfad‐Landschaften
experimentell
konstruieren.
Sie
bieten
mechanistische
Einblicke,
sich
traditionellen
Fitnesslandschaften
erheblich
unterscheiden.
einem
verwandten
Bereich
haben
Biochemiker
lange
Ergebnis
Einführung
zwei
Punktmutationen
Enzym
aus
mechanistischen
Gründen
getestet,
gefolgt
Vergleich
mit
entsprechenden
Doppelmutante
sogenannten
Doppelmutanten‐Zyklen,
additive
Effekte
zeigten.
jüngerer
Zeit
auch
hier
kooperative
antagonistische
nicht‐additive
aufgedeckt.
Wir
schließen
Vorschlägen
für
zukünftige
Arbeiten
fordern
ein
einheitliches
Gesamtbild
Epistasis.