1887

Abstract

Streptomycete bacteria are prolific producers of specialized metabolites, many of which have clinically relevant bioactivity. A striking feature of their genomes is the expansion of gene families that encode the same enzymatic function. Genes that undergo expansion events, either by horizontal gene transfer or duplication, can have a range of fates: genes can be lost, or they can undergo neo-functionalization or sub-functionalization. To test whether expanded gene families in exhibit differential expression, an RNA-Seq approach was used to examine cultures of wild-type grown with either glucose or tween as the sole carbon source.

RNA-Seq analysis showed that two-thirds of genes within expanded gene families show transcriptional differences when strains were grown on tween compared to glucose. In addition, expression of specialized metabolite gene clusters (actinorhodin, isorenieratane, coelichelin and a cryptic NRPS) was also influenced by carbon source.

Expression of genes encoding the same enzymatic function had transcriptional differences when grown on different carbon sources. This transcriptional divergence enables partitioning to function under different physiological conditions. These approaches can inform metabolic engineering of industrial strains and may help develop cultivation conditions to activate the so-called silent biosynthetic gene clusters.

Funding
This study was supported by the:
  • , Scottish Universities Life Science Alliance
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2020-03-30
2020-06-04
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References

  1. Bentley SD, Chater KF, Cerdeño-Tárraga A-M, Challis GL, Thomson NR et al. Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2). Nature 2002; 417: 141 147 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  2. Schniete JK, Cruz-Morales P, Selem-Mojica N, Fernández-Martínez LT, Hunter IS et al. Expanding Primary Metabolism Helps Generate the Metabolic Robustness To Facilitate Antibiotic Biosynthesis in Streptomyces . mBio 2018; 9: e02283 17 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  3. Nowak MA, Boerlijst MC, Cooke J, Smith JM. Evolution of genetic redundancy. Nature 1997; 388: 167 171 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  4. Wagner A. Gene duplications, robustness and evolutionary innovations. Bioessays 2008b; 30: 367 373 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  5. Wagner A. Robustness and evolvability: a paradox resolved. Proc Biol Sci 2008a; 275: 91 100 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  6. Treangen TJ, Rocha EPC. Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes. PLoS Genet 2011; 7: e1001284 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  7. Bush MJ. The actinobacterial WhiB-like (Wbl) family of transcription factors. Mol Microbiol 2018; 110: 663 676 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  8. Chater KF, Chandra G. The evolution of development in Streptomyces analysed by genome comparisons. FEMS Microbiol Rev 2006; 30: 651 672 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  9. Clark LC, Hoskisson PA. Duplication and evolution of devA-like genes in Streptomyces has resulted in distinct developmental roles. PLoS One 2011; 6: e25049 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  10. Girard G, Traag BA, Sangal V, Mascini N, Hoskisson PA et al. A novel taxonomic marker that discriminates between morphologically complex actinomycetes. Open Biol 2013; 3: 130073 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  11. Jenke-Kodama H, Sandmann A, Müller R, Dittmann E. Evolutionary implications of bacterial polyketide synthases. Mol Biol Evol 2005; 22: 2027 2039 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  12. Ridley CP, Lee HY, Khosla C. Evolution of polyketide synthases in bacteria. Proc Natl Acad Sci U S A 2008; 105: 4595 4600 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  13. Borodina I, Siebring J, Zhang J, Smith CP, van Keulen G et al. Antibiotic overproduction in Streptomyces coelicolor A3 2 mediated by phosphofructokinase deletion. J Biol Chem 2008; 283: 25186 25199 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  14. Cruz-Morales P, Kopp JF, Martínez-Guerrero C, Yáñez-Guerra LA, Selem-Mojica N et al. Phylogenomic analysis of natural products biosynthetic gene clusters allows discovery of arseno-organic metabolites in model streptomycetes. Genome Biol Evol 2016; 8: 1906 1916 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  15. Fernández-Martínez LT, Hoskisson PA. Expanding, integrating, sensing and responding: the role of primary metabolism in specialised metabolite production. Curr Opin Microbiol 2019; 51: 16 21 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  16. Noda-García L, Barona-Gómez F. Enzyme evolution beyond gene duplication: a model for incorporating horizontal gene transfer. Mob Genet Elements 2013; 3: e26439 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  17. Noda-García L, Camacho-Zarco AR, Medina-Ruíz S, Gaytán P, Carrillo-Tripp M et al. Evolution of substrate specificity in a recipient's enzyme following horizontal gene transfer. Mol Biol Evol 2013; 30: 2024 2034 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  18. Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-Scale gene function analysis with the Panther classification system. Nat Protoc 2013; 8: 1551 1566 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  19. Gubbens J, Janus M, Florea BI, Overkleeft HS, van Wezel GP. 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 2012; 86: 1490 1507 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  20. Gunnarsson N, Mortensen UH, Sosio M, Nielsen J. Identification of the Entner-Doudoroff pathway in an antibiotic-producing actinomycete species. Mol Microbiol 2004; 52: 895 902 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  21. Plou FJ, Ferrer M, Nuero OM, Calvo MV, Alcalde M et al. Analysis of Tween 80 as an esterase/ lipase substrate for lipolytic activity assay. Biotechnology Techniques 1998; 12: 183 186 [CrossRef]
    [Google Scholar]
  22. Pratt J, Cooley JD, Purdy CW, Straus DC. Lipase activity from strains of Pasteurella multocida. Curr Microbiol 2000; 40: 306 309 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  23. Sakai Y, Hayatsu M, Hayano K. Use of Tween 20 as a substrate for assay of lipase activity in soils. Soil Science and Plant Nutrition 2002; 48: 729 734 [CrossRef]
    [Google Scholar]
  24. Krügel H, Krubasik P, Weber K, Saluz HP, Sandmann G. Functional analysis of genes from Streptomyces griseus involved in the synthesis of isorenieratene, a carotenoid with aromatic end groups, revealed a novel type of carotenoid desaturase. Biochim Biophys Acta 1999; 1439: 57 64 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  25. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA. Practical Streptomyces Genetics John Innes Foundation; 2000
    [Google Scholar]
  26. Hobbs G, Frazer C, Gardner DJ, Cullum J, Oliver S. Dispersed growth of Streptomyces in liquid culture. Appl Microbiol Biotechnol 1989; 31: 272 277 [CrossRef]
    [Google Scholar]
  27. Smyth GK, Verbyla AP. A conditional likelihood approach to residual maximum likelihood estimation in generalized linear models on JSTOR. J R Stat Soc 1996; 58: 565 572 [CrossRef]
    [Google Scholar]
  28. Robinson MD, Smyth GK. Moderated statistical tests for assessing differences in tag abundance. Bioinformatics 2007; 23: 2881 2887 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
  29. Robinson MD, Smyth GK. Small-sample estimation of negative binomial dispersion, with applications to SAGE data. Biostatistics 2008; 9: 321 332 [CrossRef] [PubMed] [PubMed]
    [Google Scholar]
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