An engineered protein-phosphorylation toggle network with implications for endogenous network discovery

Deepak Mishra, Tristan Bepler, Brian Teague, Bonnie Berger, Jim Broach, Ron Weiss

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Synthetic biological networks comprising fast, reversible reactions could enable engineering of new cellular behaviors that are not possible with slower regulation. Here, we created a bistable toggle switch in Saccharomyces cerevisiae using a cross-repression topology comprising 11 protein-protein phosphorylation elements. The toggle is ultrasensitive, can be induced to switch states in seconds, and exhibits long-term bistability. Motivated by our toggle's architecture and size, we developed a computational framework to search endogenous protein pathways for other large and similar bistable networks. Our framework helped us to identify and experimentally verify five formerly unreported endogenous networks that exhibit bistability. Building synthetic protein-protein networks will enable bioengineers to design fast sensing and processing systems, allow sophisticated regulation of cellular processes, and aid discovery of endogenous networks with particular functions.

Original languageEnglish (US)
Article numbereaav0780
JournalScience
Volume373
Issue number6550
DOIs
StatePublished - Jul 2 2021

All Science Journal Classification (ASJC) codes

  • General

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