Potential of orthogonal and cross-talk quorum sensing for dynamic regulation in cocultivation

Abstract

Quorum sensing (QS) can be used to regulate bacterial population in a cell-density-dependent manner through devices such as synchronized lysis circuit (SLC) and metabolic toggle switch (MTS). However, there is still a lack of studies on cocultivation with different QS-based devices, and the widespread QS crosstalk is usually ignored in metabolic engineering. Taking microbial production of isopropanol from cellobiose with two cross-feeding strains as an example, we have mathematically modeled a comprehensive set of cocultivation configurations equipped with different QS combinations from four QS systems (lux, rpa, tra, las), with a focus on the consequence of designs with various QS crosstalk. The simulation results predict the superior performance of cocultivation with both strains adopted QS-based regulation. Furthermore, several combined QS devices with QS crosstalk could outperform the natural QS devices, and most of QS combinations with crosstalk could deliver a similar or better performance than those simulated with crosstalk ignored, thanks to the positive contribution of cross regulation in coordinating competitive growth and concomitant activation of regulated cellular processes. This work reveals theoretical potential of cocultivation with sophisticated QS-based regulation and potential value of QS devices with crosstalk in the future design of such systems.