title: A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.
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.
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain.
authors.forename: Max
authors.initials: M
authors.lastname: Carbonell-Ballestero
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain.
authors.forename: Salva
authors.initials: S
authors.lastname: Duran-Nebreda
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Montañez
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501, USA.
authors.forename: Ricard
authors.initials: R
authors.lastname: Solé
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain javier.macia@upf.edu.
authors.forename: Javier
authors.initials: J
authors.lastname: Macía
authors.affiliation: ICREA-Complex Systems Laboratory, Universitat Pompeu Fabra, 08003 Barcelona, Spain Institut de Biologia Evolutiva, CSIC-UPF, Psg. de la Barceloneta 37, 08003 Barcelona, Spain carlos.rodriguez@upf.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rodríguez-Caso
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D001665:Binding Sites; D004798:Enzymes / Q000378:metabolism; D005786:Gene Expression Regulation; D008957:Models, Genetic; D012270:Ribosomes / Q000378:metabolism; D058615:Synthetic Biology / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004798:Enzymes; D014157:Transcription Factors; C088386:homoserine lactone; D015107:4-Butyrolactone