Journal Article

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

Max Carbonell-Ballestero, Salva Duran-Nebreda, Raúl Montañez, Ricard Solé, Javier Macía and Carlos Rodríguez-Caso

in Nucleic Acids Research

Volume 42, issue 22, pages 14060-14069
Published in print December 2014 | ISSN: 0305-1048
Published online November 2014 | e-ISSN: 1362-4962 | DOI:

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  • Research Methods in Life Sciences
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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.

Journal Article.  7292 words.  Illustrated.

Subjects: Research Methods in Life Sciences ; Bioinformatics and Computational Biology