CtcS, a MarR family regulator, regulates chlortetracycline biosynthesis

Abstract

BackgroundChlortetracycline (CTC) is one of the commercially important tetracyclines (TCs) family product and is mainly produced by Streptomyces. CTC is still in a great demand due to its broad-spectrum activity against pathogens. Engineering transcriptional control allows the cell to allocate its valuable resources towards protein production and provides an important method for the build-up of desired metabolites. Despite extensive efforts concerning transcriptional regulation for increasing the productivities of TCs, the regulatory mechanisms of the CTC biosynthesis remain poorly understood.ResultsIn this study, the possible regulatory function of CtcS, a potential member of MarR (multiple antibiotic resistance regulator) family of transcriptional regulators in S. aureofaciens F3, was demonstrated. Knockdown of ctcS altered the transcription of several biosynthesis-related genes and reduced the production of tetracycline (TC) and CTC, without obvious effect on morphological differentiation and cell growth. Especially, CtcS directly repressed the transcription of the adjacent divergent gene ctcR (which encodes a putative TC resistance efflux protein). A CtcS-binding site was identified within the promoter region of ctcR by DNase I footprinting and an inverted repeat (5′-CTTGTC-3′) composed of two 6-nt half sites in the protected region was found. Moreover, both CTC and TC could attenuate the binding activity of CtcS with target DNA.ConclusionctcS regulated the production of TC and CTC in S. aureofaciens F3 and the overexpression of it could be used as a simple approach for the construction of engineering strain with higher productivity. Meanwhile, CtcS was characterized as a TC- and CTC-responsive MarR family regulator. This study provides a previously unrecognized function of CtcS and will benefit the research on the regulatory machinery of the MarR family regulators.

Positive regulation of the MarR-type regulator slnO and improvement of salinomycin production by Streptomyces albus by multiple transcriptional regulation

“…MarR regulators have been identified with antibiotic and other secondary metabolite gene clusters from Streptomyces, but only a few regulators have been characterized in the genus, including S. avermitilis SAV4189 (Guo et al 2018), S. aureofaciens F3 CtcS (Kong et al 2019), and so on.…”

Uncovering and Engineering a Mini-Regulatory Network of the TetR-Family Regulator SACE_0303 for Yield Improvement of Erythromycin in Saccharopolyspora erythraea

“…( Grove, 2013 ). In spite of abundant distribution of MFRs in the antibiotic-producing actinomycetes, just a few members have been characterized in Streptomyces ( Yang et al, 2010 ; Davis et al, 2013 ; Huang and Grove, 2013 ; Zhang et al, 2015 ; Guo et al, 2018 ; Kong et al, 2019 ; Nag and Mehra, 2021 ), and the functional probe into MFRs in Sac. erythraea has not been reported.…”

MarR Family Transcriptional Regulators and Their Roles in Plant-Interacting Bacteria

“…regulators [24,29,30] will be described in the first part of the manuscript, and then the physiological roles of these regulators in rhizospheric and endophytic bacteria will be detailed.…”

“…MarR family regulators can be classified depending on the nature of the perceived signal. Some of these regulators can bind toxic compounds like antibiotics [ 29 ] or plant-derived metabolic compounds such as phenolic molecules (salicylate, protocatechuate, p-coumarate) [ 18 , 30 , 31 , 32 ]. Other MarR-like ligands are nitrogenous derivatives: for instance, the MarR/UrtR transcriptional regulators are able to bind urate and constitute a specific subfamily [ 27 , 33 ].…”

“…The present study provides an overview of the MarR family regulators in these bacteria and whether their interactions with plants are beneficial or pathogenic. The mechanisms regulating the activity of the MarR-like transcriptional regulators [ 24 , 29 , 30 ] will be described in the first part of the manuscript, and then the physiological roles of these regulators in rhizospheric and endophytic bacteria will be detailed.…”