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Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production

  • Genomics, transcriptomics, proteomics
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A Correction to this article was published on 09 March 2020

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Abstract

Although the specific function of SCO2127 remains elusive, it has been assumed that this hypothetical protein plays an important role in carbon catabolite regulation and therefore in antibiotic biosynthesis in Streptomyces coelicolor. To shed light on the functional relationship of SCO2127 to the biosynthesis of actinorhodin, a detailed analysis of the proteins differentially produced between the strain M145 and the Δsco2127 mutant of S. coelicolor was performed. The delayed morphological differentiation and impaired production of actinorhodin showed by the deletion strain were accompanied by increased abundance of gluconeogenic enzymes, as well as downregulation of both glycolysis and acetyl-CoA carboxylase. Repression of mycothiol biosynthetic enzymes was further observed in the absence of SCO2127, in addition to upregulation of hydroxyectoine biosynthetic enzymes and SCO0204, which controls nitrite formation. The data generated in this study reveal that the response regulator SCO0204 greatly contributes to prevent the formation of actinorhodin in the ∆sco2127 mutant, likely through the activation of some proteins associated with oxidative stress that include the nitrite producer SCO0216.

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  • 09 March 2020

    The published online version of this paper contains mistake. The authors first and last names have been interchanged. The correct version is given above.

References

  • Angell S, Schwarz E, Bibb M (1992) The glucose kinase gene of Streptomyces coelicolor A3(2): its nucleotide sequence, transcriptional analysis and role in glucose repression. Mol Microbiol 6:2833–2844

    Article  CAS  PubMed  Google Scholar 

  • Angell S, Lewis C, Buttner M, Bibb M (1994) Glucose repression in Streptomyces coelicolor A3(2): a likely regulatory role for glucose kinase. Mol Gen Genet 244:135–143

    Article  CAS  PubMed  Google Scholar 

  • Arias P, Fernández-Moreno MA, Malpartida F (1999) Characterization of the pathway-specific positive transcriptional regulator for actinorhodin biosynthesis in Streptomyces coelicolor A3 ( 2 ) as a DNA-binding protein. J Bacteriol 181:6958–6968. doi:10.1038/ja.2015.13

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bentley SD, Chater KF, Cerdeño-Tárraga A-M, Challis GL, Thomson NR, James KD, Harris DE, Quail MA, Kieser H, Harper D, Bateman A, Brown S, Chandra G, Chen CW, Collins M, Cronin A, Fraser A, Goble A, Hidalgo J, Hornsby T, Howarth S, Huang C-H, Kieser T, Larke L, Murphy L, Oliver K, O’Neil S, Rabbinowitsch E, Rajandream M-A, Rutherford K, Rutter S, Seeger K, Saunders D, Sharp S, Squares R, Squares S, Taylor K, Warren T, Wietzorrek A, Woodward J, Barrell BG, Parkhill J, Hopwood DA (2002) Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2. Nature 417:141–147. doi:10.1038/417141a

    Article  PubMed  Google Scholar 

  • Bernhardt OM, Selevsek N, Gillet LC, Rinner O, Picotti P, Aebersold R, Reiter L (2012) Spectronaut: a fast and efficient algorithm for MRM-like processing of data independent acquisition (SWATH-MS) data. In: Proceedings of the 60th ASMS Conference on Mass Spectrometry and Allied Topics. Vancouver, Canada,

  • Bolstad B, Irizarry R, Astrand M, Speed T (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19:185–193

    Article  CAS  PubMed  Google Scholar 

  • Buchmeier NA, Newton GL, Koledin T, Fahey RC (2003) Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol Microbiol 47:1723–1732. doi:10.1046/j.1365-2958.2003.03416.x

    Article  CAS  PubMed  Google Scholar 

  • Bursy J, Kuhlmann AU, Pittelkow M, Hartmann H, Jebbar M, Pierik AJ, Bremer E (2008) Synthesis and uptake of the compatible solutes ectoine and 5-hydroxyectoine by Streptomyces coelicolor A3(2) in response to salt and heat stresses. Appl Environ Microbiol 74:7286–7296. doi:10.1128/AEM.00768-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bystrykh LV, Fernández-Moreno MA, Herrema JK, Malpartida F, Hopwood DA, Dijkhuizen L (1996) Production of actinorhodin-related “blue pigments” by Streptomyces coelicolor A3 ( 2 ). J Bacteriol 178:2238–2244

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chater K (2006) Streptomyces inside-out: a new perspective on the bacteria that provide us with antibiotics. Philos Trans R Soc Lond Ser B Biol Sci 361:761–768. doi:10.1098/rstb.2005.1758

    Article  CAS  Google Scholar 

  • Chávez A, García-Huante Y, Ruiz B, Langley E, Rodríguez-Sanoja R, Sanchez S (2009) Cloning and expression of the sco2127 gene from Streptomyces coelicolor M145. J Ind Microbiol Biotechnol 36:649–654. doi:10.1007/s10295-009-0533-z

    Article  PubMed  Google Scholar 

  • Chávez A, Forero A, Sánchez M, Rodríguez-Sanoja R, Mendoza-Hernández G, Servín-Gonzalez L, Sánchez B, García-Huante Y, Rocha D, Langley E, Ruiz B, Sánchez S (2011) Interaction of SCO2127 with BldKB and its possible connection to carbon catabolite regulation of morphological differentiation in Streptomyces coelicolor. Appl Microbiol Biotechnol 89:799–806. doi:10.1007/s00253-010-2905-8

    Article  PubMed  Google Scholar 

  • Cooper CE (1999) Nitric oxide and iron proteins. Biochim Biophys Acta - Bioenerg 1411:290–309. doi:10.1016/S0005-2728(99)00021-3

    Article  CAS  Google Scholar 

  • Coze F, Gilard F, Tcherkez G, Virolle M-J, Guyonvarch A (2013) Carbon-flux distribution within Streptomyces coelicolor metabolism: a comparison between the actinorhodin-producing strain M145 and its non-producing derivative M1146. PLoS One 8:e84151. doi:10.1371/journal.pone.0084151

    Article  PubMed  PubMed Central  Google Scholar 

  • Daigle F, Lerat S, Bucca G, Sanssouci É, Smith CP, Malouin F, Beaulieu C (2015) A terD domain-encoding gene (SCO2368) is involved in calcium homeostasis and participates in calcium regulation of a DosR-like regulon in Streptomyces coelicolor. J Bacteriol 197:913–923. doi:10.1128/JB.02278-14

    Article  PubMed  Google Scholar 

  • Demain, A.L Sanchez, S (2015) The need for new antibiotics. In: Sanchez, S., Demain, A.L. (Eds.), Antibiotics: current innovations and future trends, Caister Academic Press,, pp. 65–82. ISBN: 978-1-908230-54-6

  • Dietmair S, Hodson MP, Quek L-E, Timmins NE, Gray P, Nielsen LK (2012) A multi-omics analysis of recombinant protein production in Hek293 cells. PLoS One 7:e43394. doi:10.1371/journal.pone.0043394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Escher C, Reiter L, MacLean B, Ossola R, Herzog F, Chilton J, MacCoss MJ, Rinner O (2012) Using iRT, a normalized retention time for more targeted measurement of peptides. Proteomics 12:1111–1121. doi:10.1002/pmic.201100463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng WH, Mao XM, Liu ZH, Li YQ (2011) The ECF sigma factor SigT regulates actinorhodin production in response to nitrogen stress in Streptomyces coelicolor. Appl Microbiol Biotechnol 92:1009–1021. doi:10.1007/s00253-011-3619-2

    Article  CAS  PubMed  Google Scholar 

  • Fernández E, Weißbach U, Reillo CS, Braña AF, Méndez C, Rohr J, Salas JA (1998) Identification of two genes from Streptomyces argillaceus encoding glycosyltransferases involved in transfer of a disaccharide during biosynthesis of the antitumor drug mithramycin. J Bacteriol 180:4929–4937

    PubMed  PubMed Central  Google Scholar 

  • Fernández-Moreno MA, Martínez E, Boto L, Hopwood DA, Malpartida F (1992) Nucleotide sequence and deduced functions of a set of cotranscribed genes of Streptomyces coelicolor A3 (2) including the polyketide synthase for the antibiotic actinorhodin. J Biol Chem 267:19278–19290

    PubMed  Google Scholar 

  • Fernández-Moreno MA, Martínez E, Caballero JL, Ichinose K, Hopwood DA, Malpartida F (1994) DNA sequence and functions of the actVI region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2). J Biol Chem 269:24854–24863

    PubMed  Google Scholar 

  • Fischer M, Falke D, Pawlik T, Sawers RG (2014) Oxygen-dependent control of respiratory nitrate reduction in mycelium of Streptomyces coelicolor A3(2). J Bacteriol 196:4152–4162. doi:10.1128/JB.02202-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Görke B, Stülke J (2008) Carbon catabolite repression in bacteria: many ways to make the most out of nutrients. Nat Rev Microbiol 6:613–624. doi:10.1038/nrmicro1932

    Article  PubMed  Google Scholar 

  • Gubbens J, Janus M, Florea BI, Overkleeft HS, van Wezel GP (2012) Identification of glucose kinase-dependent and -independent pathways for carbon control of primary metabolism, development and antibiotic production in Streptomyces coelicolor by quantitative proteomics. Mol Microbiol 86:1490–1507. doi:10.1111/mmi.12072

    Article  CAS  PubMed  Google Scholar 

  • Gust B, Kieser T, Chater KF (2002) REDIRECT technology: PCR-targeting system in Streptomyces coelicolor. Norwich: John Innes Centre.

  • Guzman S, Carmona A, Escalante L, Imriskova I, López R, Rodrígues-Sanoja R, Ruiz B, Servín-González L, Sánchez S, Langley E (2005) Pleiotropic effect of the SCO2127 gene on the glucose uptake, glucose kinase activity and carbon catabolite repression in Streptomyces peucetius var. caesius. Microbiology 151:1717–1723. doi:10.1099/mic.0.27557-0

    Article  CAS  PubMed  Google Scholar 

  • Guzmán S, Ramos I, Moreno E, Ruiz B, Rodríguez-Sanoja R, Escalante L, Langley E, Sanchez S (2005) Sugar uptake and sensitivity to carbon catabolite regulation in Streptomyces peucetius var. caesius. Appl Microbiol Biotechnol 69:200–206. doi:10.1007/s00253-005-1965-7

    Article  PubMed  Google Scholar 

  • Hesketh A, Deery MJ, Hong H-J (2015) High-resolution mass spectrometry based proteomic analysis of the response to vancomycin-induced cell wall stress in Streptomyces coelicolor A3(2. J Proteome Res 14:2915–2928. doi:10.1021/acs.jproteome.5b00242

    Article  CAS  PubMed  Google Scholar 

  • Hodgson DA (1982) Glucose repression of carbon source uptake and metabolism in Streptomyces coelicolor A3(2) and its perturbation in mutants resistant to 2-deoxyglucose. J Gen Microbiol 128:2417–2430

    CAS  Google Scholar 

  • Hopwood DA, Sherman DH (1990) Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu Rev Genet 24:37–62

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Seno ET, Bruton CJ, Chater KF (1984) Genetic mapping, cloning and physiological aspects of the glucose kinase gene of Streptomyces coelicolor. Mol Gen Genet 196:501–507

    Article  CAS  PubMed  Google Scholar 

  • Janky R, van Helden J (2008a) RSAT-footprint-discovery. In: Regul. Seq. Anal. Tools. http://embnet.ccg.unam.mx/rsa-tools/. Accessed 1 Jan 2014

  • Janky R, van Helden J (2008b) Evaluation of phylogenetic footprint discovery for predicting bacterial cis-regulatory elements and revealing their evolution. BMC Bioinformatics 9:37. doi:10.1186/1471-2105-9-37

    Article  PubMed  PubMed Central  Google Scholar 

  • Jault JM, Fieulaine S, Nessler S, Gonzalo P, Di Pietro A, Deutscher J, Galinier A (2000) The HPr kinase from Bacillus subtilis is a homo-oligomeric enzyme which exhibits strong positive cooperativity for nucleotide and fructose 1,6-bisphosphate binding. J Biol Chem 275:1773–1780. doi:10.1074/jbc.275.3.1773

    Article  CAS  PubMed  Google Scholar 

  • Kang SH, Huang J, Lee HN, Hur YA, Cohen SN, Kim ES (2007) Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces. J Bacteriol 189:4315–4319. doi:10.1128/JB.01789-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kappler U, Nouwens AS (2013) The molybdoproteome of Starkeya novella—insights into the diversity and functions of molybdenum containing proteins in response to changing growth conditions. Metallomics 5:325–334. doi:10.1039/c2mt20230a

    Article  CAS  PubMed  Google Scholar 

  • Kieser T, Bibb M, Buttner M, Chater KF, Hopwood D (2000) Practical Streptomyces Genetics. The John Innes Foundation, Norwich

  • Lee HN, Im JH, Lee MJ, Lee SY, Kim ES (2009) A putative secreted solute binding protein, SCO6569 is a possible AfsR2-dependent down-regulator of actinorhodin biosynthesis in Streptomyces coelicolor. Process Biochem 44:373–377. doi:10.1016/j.procbio.2008.12.002

    Article  Google Scholar 

  • Licona-Cassani C, Lim S, Marcellin E, Nielsen LK (2014) Temporal dynamics of the Saccharopolyspora erythraea phosphoproteome. Mol Cell Proteomics 13:1219–1230. doi:10.1074/mcp.M113.033951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manteca A, Alvarez R, Salazar N, Yagüe P, Sanchez J (2008) Mycelium differentiation and antibiotic production in submerged cultures of Streptomyces coelicolor. Appl Environ Microbiol 74:3877–3886. doi:10.1128/AEM.02715-07

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McDonald TS, Tan KN, Hodson MP, Borges K (2014) Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides. J Cereb Blood Flow Metab 34:153–160. doi:10.1038/jcbfm.2013.184

    Article  CAS  PubMed  Google Scholar 

  • Newton GL, Buchmeier N, Fahey RC (2008) Biosynthesis and functions of mycothiol, the unique protective thiol of actinobacteria. Microbiol Mol Biol Rev 72:471–494. doi:10.1128/MMBR.00008-08

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Orellana CA, Marcellin E, Schulz BL, Nouwens AS, Gray PP, Nielsen LK (2015) High-antibody-producing chinese hamster ovary cells up-regulate intracellular protein transport and glutathione synthesis. J Proteome Res 14:609–618. doi:10.1021/pr501027c

    Article  CAS  PubMed  Google Scholar 

  • Park J-H, Cha C-J, Roe J-H (2006) Identification of genes for mycothiol biosynthesis in Streptomyces coelicolor A3(2. J Microbiol 44:121–125

    CAS  PubMed  Google Scholar 

  • Ramos I, Guzman S, Escalante L, Imriskova I, Rodriguez-Sanoja R, Sanchez S, Langley E (2004) Glucose kinase alone cannot be responsible for carbon source regulation in Streptomyces peucetius var. caesius. Res Microbiol 155:267–274. doi:10.1016/j.resmic.2004.01.004

    Article  CAS  PubMed  Google Scholar 

  • Rico S, Santamaria RI, Yepes a, Rodriguez H, Laing E, Bucca G, CP S, Diaz M (2014) Deciphering the regulon of Streptomyces coelicolor AbrC3, a positive response regulator of antibiotic production. Appl Environ Microbiol 80:2417–2428. doi:10.1128/AEM.03378-13

    Article  PubMed  PubMed Central  Google Scholar 

  • Rodríguez E, Banchio C, Diacovich L, Bibb MJ, Gramajo H (2001) Role of an essential acyl coenzyme A carboxylase in the primary and secondary metabolism of Streptomyces coelicolor A3 (2). Appl Environ Microbiol 67:4166–4176. doi:10.1128/AEM.67.9.4166

    Article  PubMed  PubMed Central  Google Scholar 

  • Roychoudhury A, Bieker A, Häussinger D, Oesterhelt F (2013) Membrane protein stability depends on the concentration of compatible solutes—a single molecule force spectroscopic study. Biol Chem 394:1465–1474. doi:10.1515/hsz-2013-0173

    Article  CAS  PubMed  Google Scholar 

  • Ruiz B, Chávez A, Forero A, García-Huante Y, Romero A, Sánchez M, Rocha D, Sánchez B, Rodríguez-Sanoja R, Langley E, Sánchez S (2010) Production of secondary metabolites: regulation by the carbon source. Crit Rev Microbiol 36:146–167

  • Sánchez B, Rodríguez-Sanoja R, Langley E, Sánchez S (2010) Production of secondary metabolites: regulation by the carbon source. Crit Rev Microbiol 36:146–167

    Article  PubMed  Google Scholar 

  • Seno ET, Chater KF (1983) Glycerol catabolic enzymes and their regulation in wild-type and mutant strains of Streptomyces coelicolor A3(2). J Gen Microbiol 129:1403–1413

    CAS  PubMed  Google Scholar 

  • Smyth G (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3:1–25

    Google Scholar 

  • Smyth G (2005) Bioinformatics and computational biology solutions using R and Bioconductor. In: Gentleman R, Carey V, Huber W, Irizarry R, Dudoit S (eds) LIMMA: linear models for microarray data. Springer, New york, pp. 397–420

    Google Scholar 

  • Taguchi T, Okamoto S, Lezhava A, Li A, Ochi K, Ebizuka Y, Ichinose K (2007) Possible involvement of ActVI-ORFA in transcriptional regulation of actVI tailoring-step genes for actinorhodin biosynthesis. FEMS Microbiol Lett 269:234–239. doi:10.1111/j.1574-6968.2007.00627.x

    Article  CAS  PubMed  Google Scholar 

  • Tsao S-W, Rudd BAM, He X-G, Chang C-J, Floss HG (1985) Identification of a red pigment from Streptomyces coelicolor A3(2) as a mixture of prodigiosin derivatives. J Antibiot (Tokyo) 38:128–131. doi:10.7164/antibiotics.38.128

    Article  CAS  Google Scholar 

  • Turatsinze J-V, Thomas-Chollier M, Defrance M, van Helden J (2008) Using RSAT to scan genome sequences for transcription factor binding sites and cis-regulatory modules. Nat Protoc 3:1578–1588. doi:10.1038/nprot.2008.97

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Shu D, Chen L, Jiang W, Lu Y (2009) Cross-talk between an orphan response regulator and a noncognate histidine kinase in Streptomyces coelicolor. FEMS Microbiol Lett 294:150–156. doi:10.1111/j.1574-6968.2009.01563.x

    Article  CAS  PubMed  Google Scholar 

  • Weiss B (2006) Evidence for mutagenesis by nitric oxide during nitrate metabolism in Escherichia coli. J Bacteriol 188:829–833. doi:10.1128/JB.188.3.829-833.2006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiśniewski JR, Zougman A, Nagaraj N, Mann M (2009) Universal sample preparation method for proteome analysis. Nat Methods 6:359–362. doi:10.1038/nmeth.1322

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr. Rosa M. Gutiérrez-Ríos and Dr. Luis Servín-González for critical reading of the manuscript. We thank Jesús Villegas, Abel Blancas, Marco A. Ortíz, and Daniel Vazquez for technical and bioinformatic support. Finally, we would like to acknowledge Dr. Mark Hudson and Dr. Amanda S. Nouwens for technical support in the proteomic experiments.

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Authors and Affiliations

  1. Instituto de Investigaciones Biomédicas. 3er Circuito Exterior s/n, Universidad Nacional Autónoma de México (UNAM), 04510, Ciudad de México, Mexico

    Tierrafría Víctor H., Maldonado-Carmona Nidia, Romero-Rodríguez Alba, Centeno-Leija Sara, Rodríguez-Sanoja Romina, Beatriz Ruiz-Villafán & Sánchez Sergio

  2. Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, St Lucia, Brisbane, Australia

    Licona-Cassani Cuauhtemoc & Marcellin Esteban

  3. Laboratorio de Bioingeniería, Universidad de Colima, Coquimatlán-, 28400, Colima, Mexico

    Nielsen Lars K.

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This work was funded by grants from DGAPA, PAPIIT, UNAM IN201413, and CONACYT CB 219686 to Sergio Sánchez. Funding agencies had no role in study design, data collection and interpretation, or the decision to submit the work for publication. This work did not involve experiments on humans or animals. The authors declare the absence of financial or non-financial competing interest. The authors alone are responsible for the content of this article. All authors have read and approved the submission.

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H., T.V., Cuauhtemoc, LC., Nidia, MC. et al. Deletion of the hypothetical protein SCO2127 of Streptomyces coelicolor allowed identification of a new regulator of actinorhodin production. Appl Microbiol Biotechnol 100, 9229–9237 (2016). https://doi.org/10.1007/s00253-016-7811-2

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