Differential contributions of two SARP family regulatory genes to indigoidine biosynthesis in Streptomyces lavendulae FRI-5

Abstract

The Streptomyces antibiotic regulatory protein (SARP) family regulators have been shown to control the production of secondary metabolites in many Streptomyces species as the most downstream regulators in the regulatory cascade. Streptomyces lavendulae FRI-5 produces a blue pigment (indigoidine) together with two types of antibiotics: D-cycloserine and the nucleoside antibiotics. The production of these secondary metabolites is governed by a signaling system consisting of a γ-butyrolactone, IM-2 [(2R,3R,1'R)-2-1'-hydroxybutyl-3-hydroxymethyl-γ-butanolide], and its cognate receptor, FarA. Here, we characterized two regulatory genes of the SARP family, farR3 and farR4, which are tandemly located in the proximal region of farA. farR3 is transcribed both as a monocistronic RNA and as a bicistronic farR4-farR3 mRNA, and the expression profile is tightly controlled by the IM-2/FarA system. Loss of farR3 delayed and decreased the production of indigoidine without any changes in the transcriptional profile of other far regulatory genes, indicating that FarR3 positively controls the biosynthesis of indigoidine and is positioned in the downstream region of the IM-2/FarA signaling system. Meanwhile, loss of farR4 induced the early production of IM-2 by increasing transcription of an IM-2 biosynthetic gene, farX, indicating that FarR4 negatively controls the biosynthesis of IM-2. Thus, our results suggested differential contributions of the SARP family regulators to the regulation of secondary metabolism in S. lavendulae FRI-5. This is the first report to show that an SARP family regulator is involved in the biosynthesis of a signaling molecule functioning at the most upstream region of the regulatory cascade for Streptomyces secondary metabolism.

The Novel Transcriptional Regulator LmbU Promotes Lincomycin Biosynthesis through Regulating Expression of Its Target Genes in Streptomyces lincolnensis

“…On the basis of their structural and functional characteristics and their amino-acid sequence similarities, these regulators are classified into several families, such as the Streptomyces antibiotic regulatory protein (SARP) family (18,19), the TetR family (20)(21)(22), and the LuxR family (23,24). However, no typical CSRs were identified in the lmb gene cluster.…”

A genomic and transcriptomic approach to investigate the blue pigment phenotype in Pseudomonas fluorescens

“…The pigmented material proved to be insoluble in water, 1 M NaOH, ethanol, methanol, acetonitrile and DMSO. In contrast indigo (Sigma 229296), indigoidine and leuco-indigoidine are freely soluble in water and DMSO (Cude et al, 2012;Kurniawan et al, 2014). The different chemical behaviors can be explained by the presence of organic substituents on the indigo molecule, which are possibly responsible of its hydrophobicity, as is the case with the indigoids studied by Starr et al (1967), which were soluble in pure TFA as well.…”

Plant growth promotion by streptomycetes: ecophysiology, mechanisms and applications

“…In Streptomyces species under nutritional stress, alarmone ppGpp plays a role as a regulator of antibiotic production [52,53]. Members of both the SARP and LAL families of regulatory proteins appear to be confined to actinobacteria, mainly genus Streptomyces, and have shown species-specific controls for secondary metabolism pathways [54][55][56]. Cell-to-cell communication is a determining factor for modulating antibiotic production, and γ-butyrolactones (GBLs) are the main intercellular signaling compounds [48].…”