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

TitleOptogenetic control of the lac operon for bacterial chemical and protein production.
Publication TypeJournal Article
Year of Publication2021
AuthorsLalwani, MA, Ip, SS, Carrasco-López, C, Day, C, Zhao, EM, Kawabe, H, Avalos, JL
JournalNat Chem Biol
Volume17
Issue1
Pagination71-79
Date Published2021 01
ISSN1552-4469
KeywordsBioreactors, Butanols, Escherichia coli, Gene Expression Regulation, Bacterial, Isopropyl Thiogalactoside, Lac Operon, Light, Light Signal Transduction, Metabolic Engineering, Mevalonic Acid, Optogenetics, Promoter Regions, Genetic
Abstract

<p>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.</p>

DOI10.1038/s41589-020-0639-1
Alternate JournalNat Chem Biol
PubMed ID32895498
Grant ListDE-SC0019363 / / DOE | SC | Biological and Environmental Research (BER) /
CBET-1751840 / / NSF | ENG/OAD | Division of Chemical, Bioengineering, Environmental, and Transport Systems (CBET) /