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DOI:

10.1111/1751-7915.12786

Authors:

V. de Lorenzo

Abstract:

From the onset of genetic engineering in the mid-70 of the last century, microbiologists have entertained programming environmental bacteria for the sake of industrial and ultimately global sustainability. The earlier agenda included not only using microorganisms as catalysts of reactions and processes alternative to those adopted by the chemical industry, but also the development of microbial agents for extensive release either to improve crop yields or for in situ bioremediation of pollutants (Lindow et al., 1989). Alas, besides early concerns on safety and the ensuing regulatory limitations about liberation of GMOs, the fact is that the scientists of the time failed to deliver much of the environmental and agricultural applications envisioned then for recombinant DNA technology. Besides encountering many unexpected microbial ecology challenges along the way (which, however, subsequently fostered new perspectives in the field that reaches us to this day), the reality of what was called at the time genetic engineering (GE) had little to do with authentic engineering. The latter is characterized by serious metrology, standards, definition of systems’ components and boundaries, transfer functions, relational logic, modularity, reusability, robust modelling and many other features that have been traditionally alien to Life Sciences research (de Lorenzo and Schmidt, 2017). In contrast, what we have generally called genetic engineering would be better described as genetic bricolage or DNA tinkering, in which genes (most often one or few at a time) are minimally manipulated and passed from their original host to another for enhancing or modifying their activity with a desired purpose. The authentic engineering aspect of such endeavours, which have dominated microbial biotechnology for decades, is close to zero: it has been just an inspiring analogy, a flamboyant metaphor – but no bona fide engineering. Although the success stories of such a trialand-error Biotechnology have been many, the time has come for a major change in the way we try to modify – and ultimately build from first principles – biological systems, in particular microorganisms. The broker of this new phase is the discipline we call Synthetic Biology (SynBio) which, capitalizing on the quantitative spirit of Systems Biology, looks at biological objects (from metabolites and proteins to whole cells) through the eyes of real (not metaphoric) engineering (Andrianantoandro et al., 2006). This involves a new interpretative frame of living entities that is compatible with, but different from, the standard evolutionary and molecular biology views that have prevailed in Biology since elucidation of the structure of DNA. While the essence of Molecular Biology relies on the so-called central dogma (DNA ? RNA ? Proteins), SynBio leaves aside the evolutionary origin of biological systems and addresses instead the compositional and relational logic that makes biological systems work the way they do. This change of perspective implies adoption of a different abstraction hierarchy, namely Parts ? Devices ? Systems. In this way, SynBio allows (i) understanding the functioning of live systems out of its physicochemical and spatial casting, (ii) modifying and combining rationally existing properties for enhancing or crafting new ones, and (iii) creating altogether new-to-nature biological activities and materials. One can immediately appreciate that the ongoing happy encounter between Life Sciences and Engineering that is the essence of SynBio can have the same profound impact in our relation with living systems as Physics had at the outset of Molecular Biology. In reality – and despite the many gaps in knowledge and multiple thus far unsolved tasks – SynBio puts in our hands an unprecedented power to revisit many of the earlier promises of GE, including those that dealt with environmental sustainability. Moreover, SynBio allows the tackling of new challenges, the scale and complexity of which previously ruled out traditional genetic engineering as a technological choice to meet them. Received 29 June, 2017; accepted 1 July, 2017. *For correspondence. E-mail vdlorenzo@cnb.csic.es; Tel. +34 91 5854536; Fax +34 91 5854506. Microbial Biotechnology (2017) 10(5), 1264–1266 doi:10.1111/1751-7915.12786 Funding Information The work is Author’s Laboratory is funded by the HELIOS Project of the Spanish Ministry of Economy and Competitiveness BIO 201566960-C3-2-R (MINECO’FEDER) and EC grants ARISYS (ERC2012-ADG-322797), EmPowerPutida (EU-H2020-BIOTEC-20142015-6335536).