Synthetic Biology Applying Engineering to Biology - Europa

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work might also yield drugs that interact with natural proteins and nucleic such in new ways, or peptide-based materials with new structures and properties. acids Schultz 39 Schultz’s group has synthesized a completely autonomous bacterium that bacteria. only genetically encodes the novel amino acid aminophenylalanine but also not it from basic carbon sources. They have extended this methodology biosynthesizes yeast cells, in which 5 non-natural amino acids have now been genetically to 1984, Benner reported the chemical synthesis of an artificial gene encoding a In enzyme. He and his coworkers introduced expanded DNA alphabets in designed and developed these into an ‘artificially expanded genetic information system’ 1989, enables the synthesis of proteins with more than 20 encoded amino acids. which 40 is exploring artificial genetic coding schemes that use non-natural Kool His group isaiming to use such approaches to engineer a new telomere- nucleotides. pathway for human cells, and they have chemically modified DNA with maintenance aim of detecting the small genetic mutations that cause cancer and drug the These are being tested for application in pathogenic bacteria resistance. 41 molecules detection of leukemias. Tirrell is combining organic, biological and for and chemistry to make new kinds of polymers with controlled architectures. In materials he pioneered the incorporation of artificial genes into microbes that particular, novel peptide sequences with interesting materials properties (for example, encode liquid-crystal phases, hydrogels, and materials for tissue engineering), as forming as developing methods for incorporating non-natural amino acids into these well (such as fluorinated variants). peptides field of metabolic engineering is traditionally close to the definition of synthetic The as it has always been aiming at creating industrial methods for the biology, of chemicals and usually also exploits rational model-supported, production rooted approaches for the design of experiments. However, as engineering engineering typically involves the exploitation of the whole cell, it also has metabolic cope with a very high complexity that is typically not well amenable to rational to In other words, it has often relied on ‘tinkering’ rather than rational analysis. engineering, frequently leading to only minor re-engineering of “design-based” properties. Nevertheless, given sufficient manpower and time, the approach cellular resulted in some very successful industrial projects with some model bacterial has in particular E. coli and B. subtilis, leading to novel production systems for systems, and fine chemicals. vitamins the approach has been extended in two directions: [i] towards the However, of novel products, most prominently the production of isoprenoid production with microbes and the production of novel pharmaceutical intermediates. derivatives projects require frequently the reassembly of alien and large pathways in These that are suitable for cheap production processes. Here, the current bacteria of genomic and metagenomic sequence data opens up novel abundance in the area of in vitro assembly of artificial biocatalytic pathways that opportunities allow novel routes to rather complex, typically pharmaceutically important, would has developed methods to genetically encode novel amino acids in encoded. f. In-cell synthesis of chemicals, materials, and biopharmaceuticals fine chemicals. [ii] Alternatively, the issue of complexity of the production system 39 http://schultz.scripps.edu 40 http://www.stanford.edu/group/kool 41 http://www.cce.caltech.edu/faculty/tirrell/research.html 28
42 addressed, as in the NEST project EUROBIOSYN . By using comprehensive can be of bacteria followed by targeted knock-outs, it is possible to create models genomic modular pathways which allow in principle realization of multi-enzyme isolated, Such pathway modules will in the future be combined to realize pathways. difficult and complex synthesis problems. particularly another EU project under the NEST synthetic biology initiative is promising Finally, help paving the road to truly personalized medicine by revolutionizing the access to hundreds of thousands of highly specific biopharmaceuticals for human therapy. to once medicines with such subtle differences can be manufactured reliably at a Only scale – something that synthetic biology could enable – is this vision small achievable. The HYBLIB project 43 aims at realizing this promise by dramatically shortening development times for specialized antibodies. 42 http://www.eurobiosyn.org 43 http://www.dkfz.de/en/b120_cbpl/mitarbeiter/frank_en.html 29
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Synthetic Biology Applying Engineering to Biology - Europa

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