Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin
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The prodigiosin biosynthetic gene cluster (pig cluster) of Serratia marcescens ATCC 274 (Sma 274) is flanked by cueR/copA homologues. Inactivation of the copA homologue resulted in an increased sensitivity to copper, confirming that CopA is involved in copper homeostasis in Sma 274. The effect of copper on the biosynthesis of prodigiosin in Sma 274 and the copA mutant strain was investigated. Increased levels of copper were found to reduce prodigiosin production in the wild type Sma 274, but increase production in the copA mutant strain. The physiological implications for CopA mediated prodigiosin production are discussed. We also demonstrate that the gene products of pigB–pigE of Sma 274 are sufficient for the biosynthesis of 2-methyl-3-n-amyl-pyrrole and condensation with 4-methoxy-2,2′-bipyrrole-5-carboxyaldehyde to form prodigiosin, as we have shown for Serratia sp. ATCC 39006.
KeywordsAntibiotic Biosynthesis Regulation Secondary metabolite
We thank Martin Welch and members of the Salmond group for helpful discussions. We would also like to thank Ian Foulds for his excellent technical assistance. This study was supported generously by the BBSRC, UK. AKPH was supported by a BBSRC studentship.
- 2.Bu’Lock JD (1961) Intermediary metabolism and antibiotic synthesis. Annu Rev Microbiol 3:293–342Google Scholar
- 6.Demain AL (1995) Why do microorganisms produce antimicrobials? In: Hunter PA, Darby GK, Russell NJ (eds) Fifty years of antimicrobials: past perspectives and future trends. Society for General Microbiology Symposium 53, Cambridge, pp 205–228Google Scholar
- 10.Harris AK, (2003) Analysis of quorum sensing and prodigiosin biosynthetic genes in Serratia marcescens. PhD thesis, Department of Biochemistry, University of CambridgeGoogle Scholar
- 16.Lowe JA, Chan YM, Tsang JC (1987) Investigation of biosynthesis of prodigiosin and its condensing enzyme in Serratia marcescens. 2. Effects of various transition metal ions. Microbios 51:71–80Google Scholar
- 27.Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning, a laboratory manual. Cold Spring Harbour Laboratory Press, New YorkGoogle Scholar
- 34.Williams RP, Quadri SM (1980) The pigments of Serratia. In: Von Graevenitz A, Rubin SJ (eds) The genus Serratia. CRC Press Inc., Boca Raton, pp 31–75Google Scholar
- 35.Williamson NR, Simonsen HT, Ahmed RAA, Goldet G, Slater H, Woodley L, Leeper FJ, Salmond GPC (2005) Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis in Streptomyces. Mol Microbiol 56:971–989CrossRefPubMedGoogle Scholar