title: Biosynthesis of the acetyl-CoA carboxylase-inhibiting antibiotic, andrimid in Serratia is regulated by Hfq and the LysR-type transcriptional regulator, AdmX.
abstract: Infections due to multidrug-resistant bacteria represent a major global health challenge. To combat this problem, new antibiotics are urgently needed and some plant-associated bacteria are a promising source. The rhizobacterium Serratia plymuthica A153 produces several bioactive secondary metabolites, including the anti-oomycete and antifungal haterumalide, oocydin A and the broad spectrum polyamine antibiotic, zeamine. In this study, we show that A153 produces a second broad spectrum antibiotic, andrimid. Using genome sequencing, comparative genomics and mutagenesis, we defined new genes involved in andrimid (adm) biosynthesis. Both the expression of the adm gene cluster and regulation of andrimid synthesis were investigated. The biosynthetic cluster is operonic and its expression is modulated by various environmental cues, including temperature and carbon source. Analysis of the genome context of the adm operon revealed a gene encoding a predicted LysR-type regulator, AdmX, apparently unique to Serratia strains. Mutagenesis and gene expression assays demonstrated that AdmX is a transcriptional activator of the adm gene cluster. At the post-transcriptional level, the expression of the adm cluster is positively regulated by the RNA chaperone, Hfq, in an RpoS-independent manner. Our results highlight the complexity of andrimid biosynthesis - an antibiotic with potential clinical and agricultural utility.
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.|Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Prof. Albareda 1, Granada, 18008, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Matilla
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
authors.forename: Veronika
authors.initials: V
authors.lastname: Nogellova
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Prof. Albareda 1, Granada, 18008, Spain.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Morel
authors.affiliation: Department of Environmental Protection, Estación Experimental del Zaidín, Consejo Superior de Investigaciones Científicas, Prof. Albareda 1, Granada, 18008, Spain.
authors.forename: Tino
authors.initials: T
authors.lastname: Krell
authors.affiliation: Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK.
authors.forename: George P C
authors.initials: GP
authors.lastname: Salmond
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D035001:Host Factor 1 Protein / Q000235:genetics / Q000378:metabolism*; D018942:Macrolides / Q000378:metabolism; D005810:Multigene Family; D011073:Polyamines / Q000378:metabolism; D011090:Polyenes / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism; D012705:Serratia / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D035001:Host Factor 1 Protein; D018942:Macrolides; D011073:Polyamines; D011090:Polyenes; D011758:Pyrroles; D014157:Transcription Factors; C547236:zeamine; C088069:andrimid; D000103:Acetyl-CoA Carboxylase