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Oct 23, 2013 (3 years and 10 months ago)

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Are we ready for…

Genome
-
scale Metabolic
Modeling
in

plants

Yoav

Teboulle

October
2012

Collakova
, E
. et al.
(
2012
). Are we ready for genome
-
scale modeling in plants?
Plant Science
,
1

18
.

Outline


Motivation


What’s been done…


Why is it tough to model plants?


What are we doing about it?


The future…







An integrated
view of
metabolism

Reductionist
studies of
individual
reactions and
pathways

Rational design
approach to
metabolic
engineering

Tinkering
approaches to
metabolic
engineering

Motivation: Why genome
-
scale
modeling?

Motivation: Why plants?



Manipulation
of plant
metabolism

Food

Feed

Fuel

Pharm

Motivation: Why plants?



Hibberd
,

J
.

M
.
,

&

Weber,

A
.

P
.

M
.

(
2012
)
.

Plant

metabolism

and

physiology
.

Current

opinion

in

plant

biology
,

15
(
3
),

225

227
.

So far: existing plant models





Arabidopsis

(
Poolman
,
2009
)

Barley

(
Grafahrend
-
Belau,
2009
)

C
4
Plants: maize,
sugarcane, sorghum


(
Dal’Molin
,
2010
)

Oilseed rape

(Hay,
2011
)

Zea

mays

(
Saha
,
2011
)

Tomato…Rice…
Lemna
…?

Is that it?! What’s so hard about
modeling plants?


Plant cell metabolism is complex…






Collectively, plants produce over

(primary
and secondary) metabolites





Proteins included
in GSMM

Genes

Base pairs

1366
(
30
%+)

4000
-
5000

4.6
M

E.coli

3500
(
10
%+)

30000

135
M

Arabidopsis

Is that it?! What’s so hard about
modeling plants?


The complexity of plant cell metabolism means
that little is known…


Experimental data is of limited coverage & bad quality



…which subsequently leads to poor annotation


Experimentally determined molecular function

~
15
%


Computationally determined molecular function

~
40
%


???







~
45
%



…which leave us with relatively poor models





Hibberd
,

J
.

M
.
,

&

Weber,

A
.

P
.

M
.

(
2012
)
.

Plant

metabolism

and

physiology
.

Current

opinion

in

plant

biology
,

15
(
3
),

225

227
.

Zhu

et

al
.
,

Elements

of

a

dynamic

systems

model

of

canopy

photosynthesis,

Current

Opinion

in

Plant

Biology,

Volume

15
,

Issue

3
,

June

2012
,

Pages

237
-
244

Is that it?! What’s so hard about
modeling plants?


Enzyme
sub
-
cellular
compartmentalization
presents another challenge in plant modeling


Duplicated pathways of central carbon metabolism, such
as glycolysis


Different organelles provide different conditions for
metabolism in terms of


pH


Salt concentrations


Energy/redox status


Transporters between organelles and cytosol need to be
identified

de

Oliveira

Dal’Molin
,

C
.

G
.
,

&

Nielsen,

L
.

K
.

(
2012
)
.

Plant

genome
-
scale

metabolic

reconstruction

and

modeling
.

Current

Opinion

in

Biotechnology,

1

7
.

Is that it?! What’s so hard about
modeling plants?


Photosynthesis & photorespiration also contribute
to the complexity…


Model assurance is unclear when dealing with tissues
whose photosynthesis is not clear
-
cut


Different pathways active in light and dark



…as do the diversity
of plant cell and tissue
types…



…which causes difficulty in the selection of
appropriate objective functions


de

Oliveira

Dal’Molin
,

C
.

G
.
,

&

Nielsen,

L
.

K
.

(
2012
)
.

Plant

genome
-
scale

metabolic

reconstruction

and

modeling
.

Current

Opinion

in

Biotechnology,

1

7
.

Excuses, you say…?

Numerous
stresses

Multiple
Objectives

Redirected
Flux

So what CAN the models do…?


Existing models are predictive where central
metabolism is concerned, less so in secondary
metabolism

These models demonstrate the applicability of
metabolic modeling approaches to plant cells…

…but still have difficulty in providing
meaningful
metabolic and mutant predictions

What are WE doing about it?

Arabidopsis

Zea

Mays

What are WE doing about it?


Two newer Arabidopsis models


AraGEM

model

(
de Oliveira
Dal’Molin
, Plant Physiology, ‘
10
)

MOm

(
Mintz
-
Oron

et al. PNAS, 2011
)

Primary

metabolism

Primary and secondary metabolism

1567 reactions

3509 reactions

1748 metabolites

2930 metabolites

cytoplasm, mitochondrion, plastid,
peroxisome
, and vacuole

cytoplasm, plastid, mitochondrion,
endoplasmic reticulum,
peroxisome
,
vacuole and
golgi
-
apparatus

Minimal medium

Rich + minimal media

What are WE doing about it?


Model improvement


Apply existing datasets



Apply novel datasets:
Asaph

Aharoni’s

Lab, Weizmann


biomass measurements


organelle
-
specific ‘
omics


gene essentiality data


flux measurements

What are WE doing about it?


Searching for ways to augment the production of:


Tocopherol

(vitamin E
)


antioxidant function


Thiamine
(vitamin B
1
)


prevention of neural and other
disorders


What are WE doing about it?


Mays model


Verification and improvement of the existing model

Saha
, R.,
Suthers
, P. F., &
Maranas
, C. D. (
2011
).
Zea

mays iRS
1563
: a comprehensive genome
-
scale metabolic
reconstruction of maize metabolism.
PloS

one
,
6
(
7
), e
21784
.



Progress to a tissue
-
specific model


Use
transcriptome

and proteome data to extract a subset of
reactions


Define tissue
-
specific biomass composition and metabolite
exchange



Increased yield in target pathways based on bacterial
gene transformation

The
FUTURE


Focus on secondary metabolism



Progress in ‘
omics

technologies



Better use of what we know!


Choose model systems we can experimentally validate


Apply known constraints


Define appropriate objective functions



Integrate regulatory mechanisms



The
FUTURE

Biomass
Production

Resistance

Stress
Tolerance

Rational Plant
Metabolic Engineering


So, are we ready for genome
-
scale modeling
in plants?


Definitely!




Questions...?




THANKS!