DNA-based assembly lines and nanofactories
Graphical abstract
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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