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Abstract
BackgroundCyclodipeptides and their derivatives constitute a large class of peptide natural products with noteworthy biological activities. In some yeasts and bacterial species, pulcherriminic acid derived from cyclo-L-leucyl-L-leucyl is excreted and chelates free ferric ions to form the pulcherrimin. In Bacillus subtilis, the enzymes YvmC and CypX are known to be involved in pulcherriminic acid biosynthesis. However, the mechanisms controlling the transcription of the yvmC-cypX operon are still unknown.ResultsIn this work, we demonstrated that the B. subtilis YvmB MarR-like regulator is the major transcription factor controlling yvmC-cypX expression. A comprehensive quantitative proteomic analysis revealed a wide and prominent effect of yvmB deletion on proteins involved in cellular processes depending on iron availability. In addition, expression of yvmB depends on iron availability. Further analysis with real-time in vivo transcriptional profiling allowed us to define the YvmB regulon. We identified yvmBA, yvmC-cypX and yvnB for negative regulation and yisI for positive regulation. In combination with genetic approaches, gel mobility shift assays indicated that a 14-bp palindromic motif constitutes the YvmB binding site. It was unexpected that YvmB controls expression of yisI, whose encoding protein plays a negative role in the regulation of the sporulation initiation pathway. YvmB appears as an additional regulatory element into the cell’s decision to grow or sporulate.ConclusionOur findings reveal a possible role of the B. subtilis YvmB regulator in the regulatory networks connected to iron metabolism and to the control of proper timing of sporulation. YvmB was renamed as PchR controlling the pulcherriminic acid biosynthetic pathway of B. subtilis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0807-3) contains supplementary material, which is available to authorized users.
Highlights
Cyclodipeptides and their derivatives constitute a large class of peptide natural products with noteworthy biological activities
We demonstrated that the uncharacterized B. subtilis YvmB MarR-type regulator is the major regulator controlling expression of the yvmCcypX operon
Inactivation of the cypX gene in ΔyvmB cells abolished red pigment production confirming that the observed red color was probably due to the presence of pulcherrimin (Fig. 2a)
Summary
Cyclodipeptides and their derivatives constitute a large class of peptide natural products with noteworthy biological activities. The mechanisms controlling the transcription of the yvmC-cypX operon are still unknown Cyclodipeptides and their derivatives constitute a large class of secondary metabolites that are mainly synthesized by microorganisms. The extended bacterial MarR family of transcriptional regulators is involved in the regulation of various cellular processes such as regulation of response to antibiotics, aromatic compounds and oxidative stress agents [17,18,19,20,21,22] They can play a crucial role in virulence factor production, enabling the pathogenic bacteria to adapt to host environments [23,24,25,26]. For many MarR-type homologues, as well as for many transcription factors, the natural ligand is still unknown
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