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Título:	A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology
Autor/a:	Carbonell Ballestero, Max, 1988-; Duran Nebreda, Salvador, 1987-; Montañez, Raúl; Solé Vicente, Ricard, 1962-; Macía, Javier; Rodríguez Caso, Carlos
Abstract:	Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined.
Abstract:	Fundacion Botín, Banco de Santander through its Santander Universities Global Division [BES-2010-038940 to/nR.M., C.R.C.]; ERC SYNCOM [291294 to M.C.B.]; FPI MINECO fellowship [to S.D.N.]. Funding for open access charge: ERC SYNCOM [291294].
Materia(s):	-Enzims
Derechos:	© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	Oxford University Press
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