Computational Tools For The Synthetic Design Of Biochemical Pathways
Enviado por Emilia06 • 10 de Marzo de 2013 • 828 Palabras (4 Páginas) • 503 Visitas
A key promise of synthetic biology is the possibility to customize the metabolic system of microorganisms
for
the
commercial
production
of
a wide
range
of
high-value
biofuels
1,2
or natural products
. Pathways for the production of alcohols, biodiesels, polyketides and terpenoids have successfully been constructed by introducing combinations of parts from various origins
into
a bacterial
host
that
is
easy
to
cultivate
3–5
. Potentially, entire metabolic pathways can be (re)
designed in silico and implemented in specialized host organisms
. Successes obtained in pioneering work on the antimalarial drug artemisinin
11–15
suggest that such approaches can be very fruitful. A biosynthetic pathway towards this compound was successfully engineered
in Saccharomyces
cerevisiae
and
Escherichia
coli
16–18
(BOX 1), and this pathway has the potential to enable much more cost-effective production of this important drug compared to the costly and laborious process of harvesting it from the source plant Artemisia annua.
The experimental work involved in engineering a synthetic pathway is considerable, and even systematically
planned
experiments
are
usually
accompanied
by
much
trial
and
error.
When
conceiving
the
design
of
a
novel
biosynthetic
pathway
(FIG. 1),
the
synthetic
biologist
has
to
find
optimal
solutions
for
selecting
pathways,
enzymes
or
host
organisms
from
an
abundance
of
possibilities.
In
this
Review,
we
explore
how
the
use
of
powerful
computational
tools
(TABLE 1)
can
lead
to
better-informed
and
more
rapid
design
and
implementation
of
novel
pathways,
and
we
propose
ways
in
which
tools
from
different
fields
of
computation
can
be
linked
together
effectively.
We
discuss
the
different
1,6–10
methodologies for identifying all possible metabolic pathways that can lead to the synthesis of a compound of choice, and how to rank these pathways based on various criteria. Subsequently, we consider how flux balance analysis of pathways can be applied to identify the most suitable candidate host organisms. We also examine how to effectively search sequence databases to obtain a list of candidate parts (such as genes and operons) for the execution of each step in the proposed
pathway.
Finally,
we
...