DNA-based assembly lines and nanofactories

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With the invention of the DNA origami technique, DNA self-assembly has reached a new level of sophistication. DNA can now be used to arrange molecules and other nanoscale components into almost arbitrary geometries  in two and even three dimensions and with nanometer precision. One exciting prospect is the realization of dynamic systems based on DNA, in which chemical reactions are precisely controlled by the spatial arrangement of components, ultimately resulting in nanoscale analogs of molecular assembly lines or ‘nanofactories’. This review will discuss recent progress toward this goal, ranging from DNA-templated synthesis over artificial DNA-based enzyme cascades to first examples of ‘molecular robots’.

Highlights

DNA nanostructures can be used to direct chemical reactions and arrange enzymes into artificial multi-enzyme complexes. ► DNA origami allows to control the three-dimensional arrangement of molecular components. ► Molecular machines, enzyme cascades, and other nanoscale components may be integrated into one system.

Section snippets

Introduction: DNA nanotechnology

Already in the early 1980s, Nadrian Seeman realized that DNA might also be used in a non-biological context  as a material for molecular ‘construction’ [1]. The basis of DNA nanotechnology is the well-known fact that two molecules of DNA pair up to form a double helix, when their base sequences are complementary. DNA duplexes are relatively rigid molecules on the nanoscale and hence are used as molecular ‘beams’ for nanoconstruction (Figure 1a). Linear assemblies are only of limited use, and so

Reaction kinetics: proximity and geometry

In biology many chemical processes occur with extraordinary specificity and efficiency. One aspect that markedly differentiates biological processes from conventional chemistry ‘in a beaker’ is spatial organization and compartmentalization. Spatial organization may influence reaction kinetics in a variety of ways. Holding two compounds in close proximity will increase the rate at which they attempt to react with each other. This is important for reactions with high activation barrier, or when

DNA-directed synthesis

There are different levels of organization that DNA nanotechnology may provide for the control of chemical reactions: proximity, spatial order in one dimension, and geometrical arrangement in two or even three dimensions. In DNA-directed synthesis, two DNA-linked reactants are brought into close proximity by hybridization to a complementary template strand (Figure 2a). This increases the effective concentration of the reagents and therefore their reaction rate [14, 15]. In principle,

Reaction cascades and multi-enzyme systems in biology

Many chemical systems in biology are organized on a scale larger than the reactive centers of single enzymes, for instance within multi-enzyme complexes. A variety of such complexes are known to carry out intricate biosynthetic tasks, for which several catalytic steps have to be performed ‘in series’, and the substrate is passed from one catalytic site to the next without escaping to the bulk phase. Such ‘channeled’ intermediates cannot participate in competing reaction pathways, and they are

Artificial enzyme cascades

The idea of artificially co-localizing enzymes to improve reaction flux has already been attempted using a variety of different approaches. Enzyme systems have been immobilized on a variety of solid matrices, resulting in an improved transfer of intermediate substrates under certain conditions [28, 29]. Other attempts were made to enforce co-localization by chemically linking several enzymes of interest to scaffolds, by recombinant engineering of fusion proteins [30], or by the utilization of

Controlling charge and energy transfer

Organization of molecules along a DNA scaffold may also be used to control other physicochemical processes that may play a role in future ‘nanofactories’. One of the visions here is to mimic biological light-harvesting complexes and also photocatalytic energy conversion such as in photosynthetic reaction centers. There are a large number of publications on the organization of chromophores and energy transfer along linear DNA scaffolds (e.g. [38, 39]), and there have been many studies on charge

Molecular robots and assembly lines

An exciting development of the past years are first attempts to couple the mechanical motion of DNA-based nanodevices to chemical synthesis. For instance, Chen and Mao showed that mechanical switching of a DNA nanodevice can be used to ‘choose’ between two alternative reactions [44]. More recently, He and Liu demonstrated how a DNA ‘walker’ autonomously performed DNA-templated multistep synthesis by carrying a DNA-linked compound through a series of reactive ‘sites’ arranged along a track [45

Conclusions

In the past years, DNA has been proven to be an extraordinary material for the assembly of complex molecular architectures. Moreover, DNA has also been shown to be capable of directing chemical reactions resulting in increased reaction efficiencies and a new approach for combinatorial chemistry. Researchers have begun to arrange enzymes into artificial reaction complexes, and DNA nanomachines have been used to control chemical synthesis and assembly processes. With the power of DNA origami,

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

The author acknowledges support through the DFG Cluster of Excellence Nanosystems Initiative Munich (NIM).

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