Structure and regulatory targets of SCO3201, a highly promiscuous TetR-like regulator of Streptomyces coelicolor M145

Xu, Delin; Waack, P.; Zhang, Qizhong; Werten, Sebastiaan; Hinrichs, W.

doi:10.1016/j.bbrc.2014.06.003

Cited by 7 publications

(10 citation statements)

References 29 publications

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“…The WhiB-like transcriptional regulator [ 35 ], WblI (SCO5046), studied in this issue was first identified as a target of the transcriptional regulator of the TetR-family (SCO3201). The over-expression of SCO3201 was shown to lead to strong repression of both antibiotic production and sporulation in S .…”

Section: Discussionmentioning

confidence: 99%

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In conditions of over-expression, WblI, a WhiB-like transcriptional regulator, has a positive impact on the weak antibiotic production of Streptomyces lividans TK24

Zhang

2017

PLoS ONE

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Regulators of the WhiB-like (wbl) family are playing important role in the complex regulation of metabolic and morphological differentiation in Streptomyces. In this study, we investigated the role of wblI, a member of this family, in the regulation of secondary metabolite production in Streptomyces lividans. The over-expression of wblI was correlated with an enhanced biosynthesis of undecylprodigiosin and actinorhodin and with a reduction of the biosynthesis of yCPK and of the grey spore pigment encoded by the whiE locus. Five regulatory targets of WblI were identified using in vitro formaldehyde crosslinking and confirmed by EMSA and qRT-PCR. These included the promoter regions of wblI itself, two genes of the ACT cluster (actVA3 and the intergenic region between the divergently orientated genes actII-1 and actII-2) and that of wblA, another member of the Wbl family. Quantitative RT-PCR analysis indicated that the expression of actVA3 encoding a protein of unknown function as well as that of actII-1, a TetR regulator repressing the expression of actII-2, encoding the ACT transporter, were down regulated in the WblI over-expressing strain. Consistently the expression of the transporter actII-2 was up-regulated. The expression of WblA, that is known to have a negative impact on ACT biosynthesis, was strongly down regulated in the WblI over-expressing strain. These data are consistent with the positive impact that WblI over-expression has on ACT biosynthesis. The latter might result from direct activation of ACT biosynthesis and export and from repression of the expression of WblA, a likely indirect, repressor of ACT biosynthesis.

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Section: Discussionmentioning

confidence: 99%

“…The putative WblI binding targets were isolated as described previously [ 35 ]. Briefly, 100~200 pmol of purified His 6 -WblI was incubated with 10 pmol of S .…”

Section: Methodsmentioning

confidence: 99%

In conditions of over-expression, WblI, a WhiB-like transcriptional regulator, has a positive impact on the weak antibiotic production of Streptomyces lividans TK24

Zhang

2017

PLoS ONE

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“…An initial crystallographic analysis of SCO3201 at 2. 1 A resolution revealed a highly asymmetric homodimer, with an unidentified small molecule bound to one of its subunits [15]. In this study, we describe a new crystal form that lacks the unknown ligand, leading to an essentially symmetric and unusually compact conformation of the dimer.…”

Section: Introductionmentioning

confidence: 88%

Crystal structures of free and ligand‐bound forms of the TetR/AcrR‐like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism

et al. 2022

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TetR/AcrR-like transcription regulators enable bacteria to sense a wide variety of chemical compounds and to dynamically adapt the expression levels of specific genes in response to changing growth conditions. Here, we describe the structural characterisation of SCO3201, an atypical TetR/ AcrR family member from Streptomyces coelicolor that strongly represses antibiotic production and morphological development under conditions of overexpression. We present crystal structures of SCO3201 in its ligand-free state as well as in complex with an unknown inducer, potentially a polyamine. In the ligand-free state, the DNA-binding domains of the SCO3201 dimer are held together in an unusually compact conformation and, as a result, the regulator cannot span the distance between the two half-sites of its operator. Interaction with the ligand coincides with a major structural rearrangement and partial conversion of the so-called hinge helix (a4) to a 3 10 -conformation, markedly increasing the distance between the DNAbinding domains. In sharp contrast to what was observed for other TetR/ AcrR-like regulators, the increased interdomain distance might facilitate rather than abrogate interaction of the dimer with the operator. Such a 'reverse' induction mechanism could expand the regulatory repertoire of the TetR/AcrR family and may explain the dramatic impact of SCO3201 overexpression on the ability of S. coelicolor to generate antibiotics and sporulate.

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“…New regulators continue to be identified: a TetR-like protein specified by Sco3201 has been found to bind to the promoters of several known developmental and antibiotic biosynthetic genes 101 , and the abrC cluster (Sco4596–8) encoding a response regulator (AbrC3) and two histidine protein kinases has been shown to influence secondary metabolism 102, 103 . An accumulation of papers has shown that the promoter of the actII-orf4 gene that activates the ACT biosynthetic genes of S. coelicolor binds at least eight, and possibly as many as 12, regulatory proteins 100 , a number to which AbrC3 has been added 103 .…”

Section: Stress Responses and Secondary Metabolismmentioning

confidence: 99%

Recent advances in understanding Streptomyces

2016

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About 2,500 papers dated 2014–2016 were recovered by searching the PubMed database for Streptomyces, which are the richest known source of antibiotics. This review integrates around 100 of these papers in sections dealing with evolution, ecology, pathogenicity, growth and development, stress responses and secondary metabolism, gene expression, and technical advances. Genomic approaches have greatly accelerated progress. For example, it has been definitively shown that interspecies recombination of conserved genes has occurred during evolution, in addition to exchanges of some of the tens of thousands of non-conserved accessory genes. The closeness of the association of Streptomyces with plants, fungi, and insects has become clear and is reflected in the importance of regulators of cellulose and chitin utilisation in overall Streptomyces biology. Interestingly, endogenous cellulose-like glycans are also proving important in hyphal growth and in the clumping that affects industrial fermentations. Nucleotide secondary messengers, including cyclic di-GMP, have been shown to provide key input into developmental processes such as germination and reproductive growth, while late morphological changes during sporulation involve control by phosphorylation. The discovery that nitric oxide is produced endogenously puts a new face on speculative models in which regulatory Wbl proteins (peculiar to actinobacteria) respond to nitric oxide produced in stressful physiological transitions. Some dramatic insights have come from a new model system for Streptomyces developmental biology, Streptomyces venezuelae, including molecular evidence of very close interplay in each of two pairs of regulatory proteins. An extra dimension has been added to the many complexities of the regulation of secondary metabolism by findings of regulatory crosstalk within and between pathways, and even between species, mediated by end products. Among many outcomes from the application of chromosome immunoprecipitation sequencing (ChIP-seq) analysis and other methods based on “next-generation sequencing” has been the finding that 21% of Streptomyces mRNA species lack leader sequences and conventional ribosome binding sites. Further technical advances now emerging should lead to continued acceleration of knowledge, and more effective exploitation, of these astonishing and critically important organisms.

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Structure and regulatory targets of SCO3201, a highly promiscuous TetR-like regulator of Streptomyces coelicolor M145

Cited by 7 publications

References 29 publications

In conditions of over-expression, WblI, a WhiB-like transcriptional regulator, has a positive impact on the weak antibiotic production of Streptomyces lividans TK24

In conditions of over-expression, WblI, a WhiB-like transcriptional regulator, has a positive impact on the weak antibiotic production of Streptomyces lividans TK24

Crystal structures of free and ligand‐bound forms of the TetR/AcrR‐like regulator SCO3201 from Streptomyces coelicolor suggest a novel allosteric mechanism

Recent advances in understanding Streptomyces

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