title: De novo design of signal sequences to localize cargo to the 1,2-propanediol utilization microcompartment.
abstract: Organizing heterologous biosyntheses inside bacterial cells can alleviate common problems owing to toxicity, poor kinetic performance, and cofactor imbalances. A subcellular organelle known as a bacterial microcompartment, such as the 1,2-propanediol utilization microcompartment of Salmonella, is a promising chassis for this strategy. Here we demonstrate de novo design of the N-terminal signal sequences used to direct cargo to these microcompartment organelles. We expand the native repertoire of signal sequences using rational and library-based approaches and show that a canonical leucine-zipper motif can function as a signal sequence for microcompartment localization. Our strategy can be applied to generate new signal sequences localizing arbitrary cargo proteins to the 1,2-propanediol utilization microcompartments.
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, 60208.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jakobson
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, 60208.|Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, California, 94720.
authors.forename: Marilyn F
authors.initials: MF
authors.lastname: Slininger Lee
authors.affiliation: Department of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, 60208.
authors.forename: Danielle
authors.initials: D
authors.lastname: Tullman-Ercek
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D016350:Leucine Zippers / Q000235:genetics; D019946:Propylene Glycol / Q000378:metabolism*; D015202:Protein Engineering; D021382:Protein Sorting Signals / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D021382:Protein Sorting Signals; D019946:Propylene Glycol
keywords: Salmonella; bacterial microcompartments; nanoreactor; signal sequence