bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Апрель 18, 2023
Abstract
Cyanobacteria
have
emerged
as
attractive
microbial
cell
factories,
they
can
convert
atmospheric
CO
2
and
sunlight
into
valuable
chemicals.
To
increase
their
growth
productivity,
one
should
aim
to
optimize
the
allocation
of
limited
cellular
resources
across
different
metabolic
processes.
Here,
we
developed
two
balance
analysis
(GBA)
models
for
cyanobacterium
Synechocystis
sp.
PCC
6803.
In
its
biological
assumptions,
closely
related
an
existing
coarse-grained
model,
while
mathematical
formulation
is
heavily
streamlined.
We
show
that
GBA
provide
virtually
identical
predictions
about
resource
among
photosynthesis,
carbon
metabolism,
protein
translation
machinery
under
environmental
conditions
previous,
mathematically
more
involved
model.
Our
model
also
captures
effects
photodamage
on
proteome
resulting
rates.
further
how
be
easily
extended
include
reactions,
leading
a
second
capable
new
allocation.
Balanced
type
presented
here
expanded
details,
providing
useful
toolbox
understanding
physiological
capabilities
cyanobacteria,
resources,
potential
bioengineering
optimized
biomass
production.
ABSTRACT
Cyanobacteria
are
photosynthetic
organisms
that
have
garnered
significant
recognition
as
potential
hosts
for
sustainable
bioproduction.
However,
their
complex
regulatory
networks
pose
challenges
to
major
metabolic
engineering
efforts,
thereby
limiting
feasibility
production
hosts.
Genome
streamlining
has
been
demonstrated
be
a
successful
approach
improving
productivity
and
fitness
in
heterotrophs
but
is
yet
explored
its
full
phototrophs.
Here,
we
present
the
systematic
reduction
of
genome
cyanobacterium
exhibiting
fastest
exponential
growth,
Synechococcus
elongatus
UTEX
2973.
This
work,
first
kind
photoautotroph,
involved
an
iterative
process
using
state-of-the-art
genome-editing
technology
guided
by
experimental
analysis
computational
tools.
CRISPR-Cas3
enabled
large,
progressive
deletions
predicted
dispensable
regions
aided
identification
essential
genes.
The
large
were
combined
obtain
strain
with
55-kb
reduction.
strains
streamlined
showed
improvement
growth
(up
23%)
(by
22.7%)
compared
wild
type
(WT).
strategy
not
only
develop
cyanobacterial
improved
traits
can
also
facilitate
better
understanding
genome-to-phenome
relationships.
IMPORTANCE
evolutionary
used
natural
living
systems
dispense
unnecessary
genes
from
mechanism
adapt
evolve.
While
this
successfully
borrowed
synthetic
heterotrophic
microbial
desired
phenotype,
it
extensively
photoautotrophs.
incorporates
both
predictions
identify
validation
tool,
study,
employed
modified
goal
minimize
size
extent
allows
optimal
cellular
under
specified
conditions.
Our
novel
tool
photoautotrophs,
which,
unlike
other
existing
tools,
enables
spontaneous
genome.
findings
demonstrate
effectiveness
obtaining
genome,
productivity.
Microbial Cell Factories,
Год журнала:
2025,
Номер
24(1)
Опубликована: Март 8, 2025
Abstract
Background
The
industrial
feasibility
of
photosynthetic
bioproduction
using
cyanobacterial
platforms
remains
challenging
due
to
insufficient
yields,
particularly
competition
between
product
formation
and
cellular
carbon
demands
across
different
temporal
phases
growth.
This
study
investigates
how
circadian
clock
regulation
impacts
partitioning
storage,
growth,
synthesis
in
Synechococcus
elongatus
PCC
7942,
provides
insights
that
suggest
potential
strategies
for
enhanced
bioproduction.
Results
After
entrainment
light-dark
cycles,
7942
cultures
transitioned
constant
light
revealed
distinct
patterns
sucrose
production,
exhibiting
three-fold
higher
productivity
during
subjective
night
compared
day
despite
moderate
down-regulation
genes
from
the
apparatus.
coincided
with
reduced
glycogen
accumulation
halted
cell
division
at
time,
suggesting
separation
competing
processes.
Transcriptome
analysis
coordinated
clock-driven
adjustment
cycle
rewiring
energy
metabolism,
over
300
showing
differential
expression
four
time
points.
was
characterized
by
altered
division-related
involved
synthesis,
while
upregulation
degradation
pathways,
alternative
electron
flow
components,
pentose
phosphate
pathway,
oxidative
decarboxylation
pyruvate.
These
molecular
changes
created
favorable
conditions
through
availability
major
precursors
(glucose-1-phosphate
fructose-6-phosphate)
maintained
redox
balance
multiple
mechanisms.
Conclusions
Our
regulatory
metabolism
balancing
suggests
two
approaches
could
be
developed
improving
bioproduction:
leveraging
natural
rhythms
optimizing
cultivation
timing
pathway
induction,
engineering
strains
mimic
circadian-driven
metabolic
shifts
controlled
flux
redistribution
rebalancing.
While
these
remain
tested,
they
theoretically
improve
efficiency
enabling
better
storage
accumulation,
phases.
Materials Today Bio,
Год журнала:
2024,
Номер
27, С. 101154 - 101154
Опубликована: Июль 14, 2024
Cyanobacteria
are
the
only
prokaryotes
capable
of
performing
oxygenic
photosynthesis
on
Earth.
Besides
their
traditional
roles
serving
as
primary
producers,
cyanobacteria
also
synthesize
abundant
secondary
metabolites
including
carotenoids,
alkaloids,
peptides,
which
have
been
reported
to
possess
medicinal
potentials.
More
importantly,
advancement
synthetic
biology
technology
has
further
expanded
potential
biomedical
applications
especially
using
living/engineered
cyanobacteria,
providing
promising
and
attractive
strategies
for
future
disease
treatments.
To
improve
understanding
facilitate
applications,
this
review
aims
discuss
current
status
prospects
cyanobacterial-based
engineering.
Firstly,
specific
properties
related
with
like
natural
products
bioactive
compounds
heavy
metal
adsorption
were
concluded.
Subsequently,
based
these
we
discussed
progress
in
various
models
hypoxia
microenvironment
alleviation,
wound
healing,
drug
delivery,
so
on.
Finally,
exploration
metabolites,
integration
synthesized
by
situ
medical
diagnosis
treatment,
optimization
vivo
application
critically
presented.
The
will
promote
studies
cyanobacteria-based
engineering
its
practical
clinical
trials
future.
The Plant Journal,
Год журнала:
2024,
Номер
119(5), С. 2500 - 2513
Опубликована: Июль 15, 2024
SUMMARY
Improvement
of
photosynthesis
requires
a
thorough
understanding
electron
partitioning
under
both
natural
and
strong
sink
conditions.
We
applied
wide
array
state‐of‐the‐art
biophysical
biochemical
techniques
to
thoroughly
investigate
the
fate
photosynthetic
electrons
in
engineered
cyanobacterium
Synechocystis
sp.
PCC
6803,
blueprint
for
biotechnology,
expressing
heterologous
gene
ene‐reductase,
YqjM.
This
recombinant
enzyme
catalyses
reduction
an
exogenously
added
substrate
into
desired
product
by
utilising
photosynthetically
produced
NAD(P)H,
enabling
whole‐cell
biotransformation.
Through
coupling
biotransformation
reaction
with
measurements,
we
demonstrated
that
artificial
sink,
outcompetes
valves,
flavodiiron
protein‐driven
Mehler‐like
cyclic
transport.
These
results
show
ferredoxin‐NAD(P)H‐oxidoreductase
is
preferred
route
delivering
from
reduced
ferredoxin
cellular
NADPH/NADP+
ratio
as
key
factor
orchestrating
flux.
insights
are
crucial
molecular
mechanisms
transport
harnessing
sustainable
bioproduction
engineering
source/sink
balance.
Furthermore,
conclude
identifying
bioenergetic
bottleneck
prerequisite
targeted
platforms.