Effects of Dual Deletion of GlnR and MtrA on Expression of Nitrogen Metabolism Genes in Streptomyces Venezuelae

Overview

Journal Microb Biotechnol

Specialties Biotechnology
Microbiology

Date 2022 Feb 11

PMID 35148463

Authors

Yanping Zhu

Jiao Wang

Wenya Su

Ting Lu

Aiying Li

Xiuhua Pang

Affiliations

Soon will be listed here.

Abstract

GlnR activates nitrogen metabolism genes under nitrogen-limited conditions, whereas MtrA represses these genes under nutrient-rich conditions in Streptomyces. In this study, we compared the transcription patterns of nitrogen metabolism genes in a double deletion mutant (ΔmtrA-glnR) lacking both mtrA and glnR and in mutants lacking either mtrA (ΔmtrA) or glnR (ΔglnR). The nitrogen metabolism genes were expressed similarly in ΔmtrA-glnR and ΔglnR under both nitrogen-limited and nutrient-rich conditions, with patterns distinctly different from that of ΔmtrA, suggesting a decisive role for GlnR in the control of nitrogen metabolism genes and further suggesting that regulation of these genes by MtrA is GlnR-dependent. MtrA and GlnR utilize the same binding sites upstream of nitrogen metabolism genes, and we showed stronger in vivo binding of MtrA to these sites under nutrient-rich conditions and of GlnR under nitrogen-limited conditions, consistent with the higher levels of MtrA or GlnR under those respective conditions. In addition, we showed that both mtrA and glnR are self-regulated. Our study provides new insights into the regulation of nitrogen metabolism genes in Streptomyces.

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References

Merrick M, Edwards R . Nitrogen control in bacteria. Microbiol Rev. 1995; 59(4):604-22. PMC: 239390. DOI: 10.1128/mr.59.4.604-622.1995. View

Ruiz-Villafan B, Cruz-Bautista R, Manzo-Ruiz M, Passari A, Villarreal-Gomez K, Rodriguez-Sanoja R . Carbon catabolite regulation of secondary metabolite formation, an old but not well-established regulatory system. Microb Biotechnol. 2021; 15(4):1058-1072. PMC: 8966007. DOI: 10.1111/1751-7915.13791. View

Tiffert Y, Supra P, Wurm R, Wohlleben W, Wagner R, Reuther J . The Streptomyces coelicolor GlnR regulon: identification of new GlnR targets and evidence for a central role of GlnR in nitrogen metabolism in actinomycetes. Mol Microbiol. 2008; 67(4):861-80. DOI: 10.1111/j.1365-2958.2007.06092.x. View

Leigh J, Dodsworth J . Nitrogen regulation in bacteria and archaea. Annu Rev Microbiol. 2007; 61:349-77. DOI: 10.1146/annurev.micro.61.080706.093409. View

Ou X, Zhang B, Zhang L, Zhao G, Ding X . Characterization of rrdA, a TetR family protein gene involved in the regulation of secondary metabolism in Streptomyces coelicolor. Appl Environ Microbiol. 2009; 75(7):2158-65. PMC: 2663221. DOI: 10.1128/AEM.02209-08. View

Voelker F, Altaba S . Nitrogen source governs the patterns of growth and pristinamycin production in 'Streptomyces pristinaespiralis'. Microbiology (Reading). 2001; 147(Pt 9):2447-2459. DOI: 10.1099/00221287-147-9-2447. View

Wang R, Mast Y, Wang J, Zhang W, Zhao G, Wohlleben W . Identification of two-component system AfsQ1/Q2 regulon and its cross-regulation with GlnR in Streptomyces coelicolor. Mol Microbiol. 2012; 87(1):30-48. DOI: 10.1111/mmi.12080. View

Yan H, Lu X, Sun D, Zhuang S, Chen Q, Chen Z . BldD, a master developmental repressor, activates antibiotic production in two Streptomyces species. Mol Microbiol. 2019; 113(1):123-142. DOI: 10.1111/mmi.14405. View

Zhang P, Zhao Z, Li H, Chen X, Deng Z, Bai L . Production of the antibiotic FR-008/candicidin in Streptomyces sp. FR-008 is co-regulated by two regulators, FscRI and FscRIV, from different transcription factor families. Microbiology (Reading). 2015; 161(Pt 3):539-52. DOI: 10.1099/mic.0.000033. View

10.

Martin J, Liras P . The Balance Metabolism Safety Net: Integration of Stress Signals by Interacting Transcriptional Factors in and Related Actinobacteria. Front Microbiol. 2020; 10:3120. PMC: 6988585. DOI: 10.3389/fmicb.2019.03120. View

11.

Fink D, Weissschuh N, Reuther J, Wohlleben W, Engels A . Two transcriptional regulators GlnR and GlnRII are involved in regulation of nitrogen metabolism in Streptomyces coelicolor A3(2). Mol Microbiol. 2002; 46(2):331-47. DOI: 10.1046/j.1365-2958.2002.03150.x. View

12.

Frojd M, Flardh K . Apical assemblies of intermediate filament-like protein FilP are highly dynamic and affect polar growth determinant DivIVA in Streptomyces venezuelae. Mol Microbiol. 2019; 112(1):47-61. DOI: 10.1111/mmi.14253. View

13.

Bush M, Chandra G, Al-Bassam M, Findlay K, Buttner M . BldC Delays Entry into Development To Produce a Sustained Period of Vegetative Growth in Streptomyces venezuelae. mBio. 2019; 10(1). PMC: 6428758. DOI: 10.1128/mBio.02812-18. View

14.

He J, Zhu H, Zheng G, Liu P, Wang J, Zhao G . Direct Involvement of the Master Nitrogen Metabolism Regulator GlnR in Antibiotic Biosynthesis in Streptomyces. J Biol Chem. 2016; 291(51):26443-26454. PMC: 5159505. DOI: 10.1074/jbc.M116.762476. View

15.

Wang J, Wang Y, Zhao G . Precise characterization of GlnR Box in actinomycetes. Biochem Biophys Res Commun. 2015; 458(3):605-607. DOI: 10.1016/j.bbrc.2015.02.010. View

16.

Zhu Y, Wang J, Su W, Lu T, Li A, Pang X . Effects of dual deletion of glnR and mtrA on expression of nitrogen metabolism genes in Streptomyces venezuelae. Microb Biotechnol. 2022; 15(6):1795-1810. PMC: 9151340. DOI: 10.1111/1751-7915.14016. View

17.

Hoskisson P, Fernandez-Martinez L . Regulation of specialised metabolites in Actinobacteria - expanding the paradigms. Environ Microbiol Rep. 2018; 10(3):231-238. PMC: 6001450. DOI: 10.1111/1758-2229.12629. View

18.

Zhu Y, Zhang P, Zhang J, Xu W, Wang X, Wu L . The developmental regulator MtrA binds GlnR boxes and represses nitrogen metabolism genes in Streptomyces coelicolor. Mol Microbiol. 2019; 112(1):29-46. DOI: 10.1111/mmi.14252. View

19.

Lu T, Cao Q, Pang X, Xia Y, Xun L, Liu H . Sulfane sulfur-activated actinorhodin production and sporulation is maintained by a natural gene circuit in Streptomyces coelicolor. Microb Biotechnol. 2020; 13(6):1917-1932. PMC: 7533328. DOI: 10.1111/1751-7915.13637. View

20.

Singh K, Athira P, Bhardwaj N, Singh D, Watson U, Kumar Saini D . Acetylation of Response Regulator Protein MtrA in Regulates Its Repressor Activity. Front Microbiol. 2021; 11:516315. PMC: 7843721. DOI: 10.3389/fmicb.2020.516315. View