Optogenetic control of the lac operon for bacterial chemical and protein production

Control of thelacoperon with isopropyl beta-d-1-thiogalactopyranoside (IPTG) has been used to regulate gene expression inEscherichia colifor countless applications, including metabolic engineering and recombinant protein production. However, optogenetics offers unique capabilities, such as easy tunability, reversibility, dynamic induction strength and spatial control, that are difficult to obtain with chemical inducers. We have developed a series of circuits for optogenetic regulation of thelacoperon, which we call OptoLAC, to control gene expression from various IPTG-inducible promoters using only blue light. Applying them to metabolic engineering improves mevalonate and isobutanol production by 24% and 27% respectively, compared to IPTG induction, in light-controlled fermentations scalable to at least two-litre bioreactors. Furthermore, OptoLAC circuits enable control of recombinant protein production, reaching yields comparable to IPTG induction but with easier tunability of expression. OptoLAC circuits are potentially useful to confer light control over other cell functions originally designed to be IPTG-inducible.

Automated summary

By using OptoLAC circuits for light-controlled gene expression, improved metabolic engineering production and easier tunability of recombinant protein production can be achieved compared to IPTG induction.