Abstract
Bacteria can be harnessed to synthesise high-value chemicals. A promising strategy for increasing productivity uses inducible control systems to switch metabolism from growth to chemical synthesis once a large population of cell factories are generated. However, use of expensive chemical inducers limits scalability of this approach for biotechnological applications. Switching using cheap nutrients is an appealing alternative, but their tightly regulated uptake and consumption again limits scalability. Here, using mathematical models of fatty acid uptake in E. coli as an exemplary case study, we unravel how the cell’s native regulation and program of induction can be engineered to minimise inducer usage. We show that integrating positive feedback loops into the circuitry creates an irreversible metabolic switch, which, requiring only temporary induction, drastically reduces inducer usage. Our proposed switch should be widely applicable, irrespective of the product of interest, and brings closer the realization of scalable and sustainable microbial chemical production.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Additional study and discussion comparing and contrasting performance of the proposed oleic acid-inducible irreversible switch with application of the IPTG-inducible canonical toggle switch for dynamic control. Additional results added to final results subsection; extended discussion to detail economic implications of nutrient-inducible irreversible switch use, and additional supplementary note S10 on the formulation and analysis of applying the canonical toggle switch for dynamic control.