A GntR family transcriptional regulator (PigT) controls gluconate-mediated repression and defines a new, independent pathway for regulation of the tripyrrole antibiotic, prodigiosin, in Serratia

Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK Correspondence George P. C. Salmond gpcs{at}mole.bio.cam.ac.uk Biosynthesis of the red, tripyrrole antibiotic prodigiosin (Pig) by Serratia sp. ATCC 39006 (39006) is controlled by a complex regulatory network involving an N -acyl homoserine lactone ( N -AHL) quorum-sensing system, at least two separate two-component signal transduction systems and a multitude of other regulators. In this study, a new transcriptional activator, PigT, and a physiological cue (gluconate), which are involved in an independent pathway controlling Pig biosynthesis, have been characterized. PigT, a GntR homologue, activates transcription of the pigA–O biosynthetic operon in the absence of gluconate. However, addition of gluconate to the growth medium of 39006 repressed transcription of pigA–O , via a PigT-dependent mechanism, resulting in a decrease in Pig production. Finally, expression of the pigT transcript was shown to be maximal in exponential phase, preceding the onset of Pig production. This work expands our understanding of both the physiological and genetic factors that impinge on the biosynthesis of the secondary metabolite Pig in 39006. Abbreviations: 39006, Serratia sp. ATCC 39006; BHL, N -butanoyl- L -homoserine lactone; Car, carbapenem; CRP, cAMP receptor protein; HHL, N -hexanoyl- L -homoserine lactone; HTH, helix–turn–helix; N -AHL, N -acyl homoserine lactone; Pig, prodigiosin; QS, quorum sensing; RBS, ribosome-binding site; WT, wild-type The GenBank/EMBL/DDBJ accession number for the pigT ORF sequence reported in this paper is AJ973142 .