Role of the phosphopantetheinyltransferase enzyme, PswP, in the biosynthesis of antimicrobial secondary metabolites by Serratia marcescens Db10.
Phosphopantetheinyltransferase (PPTase) enzymes fulfil essential roles in primary and secondary metabolism in prokaryotes, archaea and eukaryotes. PPTase enzymes catalyse the essential modification of the carrier protein domain of fatty acid synthases, polyketide synthases (PKSs) and non-ribosomal peptide synthetases (NRPSs). In bacteria and fungi, NRPS and PKS enzymes are often responsible for the biosynthesis of secondary metabolites with clinically relevant properties; these secondary metabolites include a variety of antimicrobial peptides. We have previously shown that in the Gram-negative bacterium Serratia marcescens Db10, the PPTase enzyme PswP is essential for the biosynthesis of an NRPS-PKS dependent antibiotic called althiomycin. In this work we utilize bioinformatic analyses to classify PswP as belonging to the F/KES subfamily of Sfp type PPTases and to putatively identify additional NRPS substrates of PswP, in addition to the althiomycin NRPS-PKS, in Ser. marcescens Db10. We show that PswP is required for the production of three diffusible metabolites by this organism, each possessing antimicrobial activity against Staphylococcus aureus. Genetic analyses identify the three metabolites as althiomycin, serrawettin W2 and an as-yet-uncharacterized siderophore, which may be related to enterobactin. Our results highlight the use of an individual PPTase enzyme in multiple biosynthetic pathways, each contributing to the ability of Ser. marcescens to inhibit competitor bacteria by the production of antimicrobial secondary metabolites.
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Amy J
AJ
Gerc
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Nicola R
NR
Stanley-Wall
Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Sarah J
SJ
Coulthurst
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000378:metabolism / Q000494:pharmacology; D064210:Secondary Metabolism; D012706:Serratia marcescens / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000378:metabolism / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008074:Lipoproteins; D010456:Peptides, Cyclic; D017262:Siderophores; D013844:Thiazoles; C082662:phosphopantetheinyl transferase; C010018:althiomycin; C073497:serrawettin W2; D017855:Transferases (Other Substituted Phosphate Groups)