Easac'10 sb indd

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.

---