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

作者：Carbonell Ballestero Max; Duran Nebreda Salva; Montanez Raul; Sole Ricard; Macia Javier^*; Rodriguez Caso Carlos

来源：Nucleic Acids Research, 2014, 42(22): 14060-14069.

DOI：10.1093/nar/gku964

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%26apos;s ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined.

• 出版日期2014-12-16