Mathematical Modeling of a Bioluminescent E. Coli Based Biosensor

In this work we present a mathematical model for the bioreporter activity of an E. coli based bioluminescent bioreporter. This bioreporter is based on a genetically modified E. coli which harbors the recA promoter, a member of the bacterial SOS response, fused to the bacterial luminescence (lux) genes. This bioreporter responds to the presence of DNA damaging agents such as heavy metals, H2O2 and Nalidixic Acid (NA) that activate the SOS response. In our mathematical model we implemented basic physiological mechanisms such as: the penetration of the NA into the biosensor; gyrase enzyme inhibition by the NA; gyrase level regulation; creation of chromosomal DNA damage; DNA repair and release of ssDNA into the cytoplasm; SOS induction and chromosomal DNA repair; activation of lux genes by the fused recA promoter carried on a plasmidal DNA; transcription and translation of the luminescence responsible enzymes; luminescence cycle; energy molecules level regulation and the regulation of the O-2 consumption. The mathematical model was defined using a set of ordinary differential equations (ODE) and solved numerically. We simulated the system for different concentrations of NA in water for specific biosensors concentration, and under limited O-2 conditions. The simulated results were compared to experimental data and satisfactory matching was obtained. This manuscript presents a proof of concept showing that real biosensors can be modeled and simulated. This sets the ground to the next stage of implementing a comprehensive physiological model using experimentally extracted parameters. Following the completion of the next stage, it will be possible to construct a "Computer Aided Design" tool for the simulation of the genetically engineered biosensors. We define a term "bioCAD" for a Biological System Computer Aided Design. The specific bioCAD that is described here is aimed towards whole cell biosensors which are under investigation today for functional sensing. Usage of the bioCAD will improve the biosensors design process and boost their performance. It will also reduce Non Recurring Engineering (NRE) cost and time. Finally, using a parameterized solution will allow fair and quick evaluation of whole cell biosensors for various applications.