Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 1, 2024
Spatial
organization
of
microbes
in
biofilms
enables
crucial
community
function
such
as
division
labor.
However,
quantitative
understanding
emergent
properties
remains
limited
due
to
a
scarcity
tools
for
patterning
heterogeneous
biofilms.
Here
we
develop
synthetic
optogenetic
toolkit
'Multipattern
Biofilm
Lithography'
rational
engineering
and
orthogonal
multi-strain
biofilms,
inspired
by
successive
adhesion
phenotypic
differentiation
natural
We
apply
this
profile
the
growth
dynamics
biofilm
communities,
observe
emergence
spatially
modulated
commensal
relationships
shared
antibiotic
protection
against
beta-lactam
ampicillin.
Supported
biophysical
modeling,
these
results
yield
in-vivo
measurements
key
parameters,
e.g.,
molecular
beta-lactamase
production
per
cell
length
scale
zone
protection.
Our
toolbox
associated
findings
provide
insights
into
spatial
distributed
within
with
direct
implications
future
research
engineering.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 24, 2024
Abstract
Discrepancy
between
model
predictions
and
actual
processes,
known
as
process–model
mismatch
(PMM),
remains
a
serious
challenge
in
bioprocess
optimization.
Previously,
we
proposed
the
hybrid
silico/in-cell
controller
(HISICC)
concept
combining
model-based
optimization
with
cell-based
feedback
to
address
PMM
problem.
Herein,
this
approach
was
advanced
regulate
intracellular
concentrations
of
rate-limiting
enzymes.
Advanced
HISICC
demonstrated
using
an
engineered
Escherichia
coli
strain
for
fatty
acid
production
(FA3).
This
harbors
in-cell
controller,
which
decelerates
acetyl-CoA
carboxylase
(ACC)
overexpression
response
sensing
concentration
malonyl-CoA
formed
by
enzyme.
A
mathematical
FA3
constructed
validated
experimental
data.
Simulations
assuming
various
revealed
that
effectively
mitigates
toxicity
from
excessive
ACC
robustly
adapting
braking
its
overexpression,
minimizing
yield
loss.
study
confirmed
viable
strategy
enhancing
efficiency,
especially
balancing
bottleneck
enzyme
levels.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Ноя. 1, 2024
Spatial
organization
of
microbes
in
biofilms
enables
crucial
community
function
such
as
division
labor.
However,
quantitative
understanding
emergent
properties
remains
limited
due
to
a
scarcity
tools
for
patterning
heterogeneous
biofilms.
Here
we
develop
synthetic
optogenetic
toolkit
'Multipattern
Biofilm
Lithography'
rational
engineering
and
orthogonal
multi-strain
biofilms,
inspired
by
successive
adhesion
phenotypic
differentiation
natural
We
apply
this
profile
the
growth
dynamics
biofilm
communities,
observe
emergence
spatially
modulated
commensal
relationships
shared
antibiotic
protection
against
beta-lactam
ampicillin.
Supported
biophysical
modeling,
these
results
yield
in-vivo
measurements
key
parameters,
e.g.,
molecular
beta-lactamase
production
per
cell
length
scale
zone
protection.
Our
toolbox
associated
findings
provide
insights
into
spatial
distributed
within
with
direct
implications
future
research
engineering.
