title: Investigating lipoprotein biogenesis and function in the model Gram-positive bacterium Streptomyces coelicolor.
abstract: Lipoproteins are a distinct class of bacterial membrane proteins that are translocated across the cytoplasmic membrane primarily by the Sec general secretory pathway and then lipidated on a conserved cysteine by the enzyme lipoprotein diacylglycerol transferase (Lgt). The signal peptide is cleaved by lipoprotein signal peptidase (Lsp) to leave the lipid-modified cysteine at the N-terminus of the mature lipoprotein. In all Gram-positive bacteria tested to date this pathway is non-essential and the lipid attaches the protein to the outer leaflet of the cytoplasmic membrane. Here we identify lipoproteins in the model Gram-positive bacterium Streptomyces coelicolor using bioinformatics coupled with proteomic and downstream analysis. We report that Streptomyces species translocate large numbers of lipoproteins out via the Tat (twin arginine translocase) pathway and we present evidence that lipoprotein biogenesis might be an essential pathway in S. coelicolor. This is the first analysis of lipoproteins and lipoprotein biogenesis in Streptomyces and provides the first evidence that lipoprotein biogenesis could be essential in a Gram-positive bacterium. This report also provides the first experimental evidence that Tat plays a major role in the translocation of lipoproteins in a specific bacterium.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Thompson
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Widdick
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Hicks
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Govind
authors.initials: G
authors.lastname: Chandra
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Sutcliffe
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Tracy
authors.initials: T
authors.lastname: Palmer
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, UK.Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.School of Applied Sciences, Northumbria University, Newcastle NE1 8ST, UK.School of Medicine, Health Policy and Practice, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Matthew I
authors.initials: MI
authors.lastname: Hutchings
mesh_terms: D019295:Computational Biology; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D020543:Proteome / Q000032:analysis; D048372:Streptomyces coelicolor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008074:Lipoproteins; D020543:Proteome