Optogenetic control of the lac operon for bacterial chemical and protein production. Author Makoto Lalwani, Samantha Ip, César Carrasco-López, Catherine Day, Evan Zhao, Hinako Kawabe, José Avalos Publication Year 2021 Type Journal Article Abstract Control of the lac operon with isopropyl β-D-1-thiogalactopyranoside (IPTG) has been used to regulate gene expression in Escherichia coli for 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 the lac operon, 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. Keywords Gene Expression Regulation, Bacterial, Escherichia coli, Promoter Regions, Genetic, Light Signal Transduction, Light, Optogenetics, Lac Operon, Butanols, Metabolic Engineering, Bioreactors, Isopropyl Thiogalactoside, Mevalonic Acid Journal Nat Chem Biol Volume 17 Issue 1 Pages 71-79 Date Published 2021 Jan ISSN Number 1552-4469 DOI 10.1038/s41589-020-0639-1 Alternate Journal Nat Chem Biol PMCID 5876151 PMID 32895498 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML