14
| December 2010 | Realising European
potential in synthetic biology
EASAC
biosynthetic pathways. Thus, this fi eld is entering a new
dimension in terms of generating products from complex
gene clusters rather than a single gene. It can be expected
that such products will become less expensive than when
produced by conventional routes and that, in many cases,
there will be environmental advantages in sustainable
chemistry
17
. One particularly interesting example is
offered by the engineering
of non-ribosomal peptides of
polyketides in bacteria on naturally modular assembly-line
multi-enzymes. Many of the natural products of these
multi-enzyme systems are clinically validated drugs, and
rational redesign of these pathways appears to offer a
relatively near-term societal and commercial benefi t from
synthetic biology in the shape of improved antibiotics and
other bioactive natural products (Zhang et al. 2008).
5.5 Protocells
By contrast with the approach based on reducing
biological systems, researchers are also attempting to
create synthetic cells de novo by programmable chemical
design, i.e. from inorganic as well as organic molecules.
The ambitious objective is for such cells to have
properties of self-repair, self-assembly, self-reproduction
and evolvability (Rasmussen et al. 2004). Whereas the
biological community dominates the various work on
systems in vivo, the research on protocells is strongly
supported by the chemistry, physics and bioinformatics
communities.
Signifi cant progress has been achieved in the Framework
Programme 6 project, PACE (Programmable Artifi cial
Cell Evolution, www.istpace.org). The protocell
model can be viewed as an enclosed laboratory to
study chemical reactions in confi ned geometries and
depends on integration of lipid metabolism (the basis
for cell containment), genetic information (the basis
for replicability) and redox metabolism (for energy
production). There is the prospect that methodological
advances will allow the same high information density
in chemical processing as is found in living cells. One
experimental challenge is to create selective membrane
permeability and, in part, this research can build on the
considerable European experience on artifi cial vesicles
and the understanding of membrane function. For
example, semi-synthetic membrane systems have been
constructed with channels that can be controlled using
light or pH change (Kocer et al. 2007).
Other European-funded work on semi-synthetic minimal
cells, the ‘Minimal Life Project’ (Chiarabelli et al. 2009),
exemplifi es the potential for novel applications, for
example in drug delivery systems, where the drug
is produced within the minimal cell compartment.
Such work is also helping to identify those essential
characteristics of minimal cells that enable them to
reproduce, interact with the environment and evolve.
In parallel with the technical work on development
of artifi cial cells, the EU is supporting efforts to foster
informed public discussion about the social, safety
and ethical issues that may be raised by these specifi c
developments (European Centre for Living Technology,
www.ecltech.org). In time, many assume that research
on artifi cial life will illuminate the perennial questions
such as ‘what is life?’ (Rasmussen et al. 2004)
18
. In
the meantime, however, there
are some very practical
questions to be answered. What are the obstacles to
integrating genes, proteins and energetics within a
container? How can theory and simulation better inform
experiments? What are the most likely early applications
of this research? Work on protocells is helping to
understand how natural self-replicating systems emerge
but can also be expected to lead to the engineering of
self-replicating machines.
5.6 Bionanoscience
Biological cells are equipped with a variety of molecular
machines that perform complex tasks such as cell
division and intracellular transport. It is envisaged
that analogues of these biological motors could be
employed in artifi cial environments (Van den Heuvel
and Dekker 2007) in cells or cell-free devices. Proof-of-
principle for a variety of systems has been demonstrated
in a series of publications from researchers in the
Netherlands, described in the Netherlands Academy’s
report, using motor proteins (particularly kinesin-
or myosin-based) for manipulating and powering
nanoscale components, a key step in the development
of nanomachines. For example, molecular-scale motors
can be light-driven (Eelkema et al. 2006) or constructed
as controlled biohybrid motors where enzymes working
in tandem create kinetic energy (Pantarotto et al.
2008)
19
. The bionanosciences are likely to deliver many
other applications, for example in biosensing and
catalysis.
17
One illustration of the magnitude of these opportunities for sustainable chemistry is provided by the diverse natural landscape
represented by secondary metabolites in symbiotic bacteria (Piel 2009). Current extraction of drugs and other chemicals from
such sources in their natural habitat is unsustainable.
18
EASAC member academies continue to stimulate discussion on these fundamental issues. For example, ‘What is life?’ is the
title of the Leopoldina biennial assembly to be held on 23–25 September 2011 (www.leopoldina-halle.de).
19
Biohybrid motor systems are an active area of research elsewhere in the EU, for example funded by the Framework Programme
6 Network of Excellence MAGMANET. In a recent publication (Lee et al. 2009), it was noted that research on molecular
machines has been impeded because most such molecules have been organic whereas the physical properties that are most
desirable in molecular machines – such as magnetism or the ability to conduct electrons – are usually found in inorganic
compounds. This obstacle is being overcome by research on biohybrids.