Skip to main content
SpringerLink
Log in

Genome-guided discovery of diverse natural products from Burkholderia sp.

  • Mini-Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Burkholderia species have emerged as a new source of diverse natural products. This mini-review covers all of the natural products discovered in recent years from Burkholderia sp. by genome-guided approaches—these refer to the use of bacterial genome sequence as an entry point for in silico structural prediction, wet lab experimental design, and execution. While reliable structural prediction based on cryptic biosynthetic gene cluster sequence was not always possible due to noncanonical domains and/or module organization of a deduced biosynthetic pathway, a molecular genetic method was often employed to detect or alter the expression level of the gene cluster to achieve an observable phenotype, which facilitated downstream natural product purification and identification. Those examples of natural product discovery from Burkholderia sp. provide practical guidance for future exploration of Gram-negative bacteria as a new source of natural products.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Bayro MJ, Mukhopadhyay J, Swapna GV, Huang JY, Ma LC, Sineva E, Dawson PE, Montelione GT, Ebright RH (2003) Structure of antibacterial peptide microcin J25: a 21-residue lariat protoknot. J Am Chem Soc 125:12382–12383

    Article  CAS  PubMed  Google Scholar 

  2. Biggins JB, Gleber CD, Brady SF (2011) Acyldepsipeptide HDAC inhibitor production induced in Burkholderia thailandensis. Org Lett 13:1536–1539

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Biggins JB, Liu X, Feng Z, Brady SF (2011) Metabolites from the induced expression of cryptic single operons found in the genome of Burkholderia pseudomallei. J Am Chem Soc 133:1638–1641

    Article  CAS  PubMed  Google Scholar 

  4. Biggins JB, Ternei MA, Brady SF (2012) Malleilactone, a polyketide synthase-derived virulence factor encoded by the cryptic secondary metabolome of Burkholderia pseudomallei group pathogens. J Am Chem Soc 134:13192–13195

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Blin K, Medema MH, Kazempour D, Fischbach MA, Breitling R, Takano E, Weber T (2013) antiSMASH 2.0–a versatile platform for genome mining of secondary metabolite producers. Nucleic Acids Res 41:W204–W212

    Article  PubMed Central  PubMed  Google Scholar 

  6. Brady SF, Bauer JD, Clarke-Pearson MF, Daniels R (2007) Natural products from isnA-containing biosynthetic gene clusters recovered from the genomes of cultured and uncultured bacteria. J Am Chem Soc 129:12102–12103

    Article  CAS  PubMed  Google Scholar 

  7. Carr G, Seyedsayamdost MR, Chandler JR, Greenberg EP, Clardy J (2011) Sources of diversity in bactobolin biosynthesis by Burkholderia thailandensis E264. Org Lett 13:3048–3051

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Challis GL (2008) Genome mining for novel natural product discovery. J Med Chem 51:2618–2628

    Article  CAS  PubMed  Google Scholar 

  9. Cheng Y-Q, Yang M, Matter AM (2007) Characterization of a gene cluster responsible for the biosynthesis of anticancer agent FK228 in Chromobacterium violaceum No. 968. Appl Environ Microbiol 73:3460–3469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Coenye T, Vandamme P (2003) Diversity and significance of Burkholderia species occupying diverse ecological niches. Environ Microbiol 5:719–729

    Article  CAS  PubMed  Google Scholar 

  11. Compant S, Nowak J, Coenye T, Clement C, Ait Barka E (2008) Diversity and occurrence of Burkholderia spp. in the natural environment. FEMS Microbiol Rev 32:607–626

    Article  CAS  PubMed  Google Scholar 

  12. Corre C, Challis GL (2009) New natural product biosynthetic chemistry discovered by genome mining. Nat Prod Rep 26:977–986

    Article  CAS  PubMed  Google Scholar 

  13. Dance DA (2002) Melioidosis. Curr Opin Infect Dis 15:127–132

    Article  PubMed  Google Scholar 

  14. Darst SA (2004) New inhibitors targeting bacterial RNA polymerase. Trends Biochem Sci 29:159–160

    Article  CAS  PubMed  Google Scholar 

  15. Dvorak GD, Spickler AR (2008) Glanders. J Am Vet Med Assoc 233:570–577

    Article  PubMed  Google Scholar 

  16. El-Elimat T, Figueroa M, Raja HA, Graf TN, Adcock AF, Kroll DJ, Day CS, Wani MC, Pearce CJ, Oberlies NH (2013) Benzoquinones and terphenyl compounds as phosphodiesterase-4B inhibitors from a fungus of the order Chaetothyriales (MSX 47445). J Nat Prod 76:382–387

    Article  CAS  PubMed  Google Scholar 

  17. Franke J, Ishida K, Hertweck C (2012) Genomics-driven discovery of burkholderic acid, a noncanonical, cryptic polyketide from human pathogenic Burkholderia species. Angew Chem Int Ed 51:11611–11615

    Article  CAS  Google Scholar 

  18. Furumai R, Matsuyama A, Kobashi N, Lee KH, Nishiyama M, Nakajima H, Tanaka A, Komatsu Y, Nishino N, Yoshida M, Horinouchi S (2002) FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 62:4916–4921

    CAS  PubMed  Google Scholar 

  19. Galyov EE, Brett PJ, DeShazer D (2010) Molecular insights into Burkholderia pseudomallei and Burkholderia mallei pathogenesis. Annu Rev Microbiol 64:495–517

    Article  CAS  PubMed  Google Scholar 

  20. Garcia-Osta A, Cuadrado-Tejedor M, Garcia-Barroso C, Oyarzabal J, Franco R (2012) Phosphodiesterases as therapeutic targets for Alzheimer’s disease. ACS Chem Neurosci 3:832–844

    Article  CAS  PubMed  Google Scholar 

  21. Hegemann JD, Zimmermann M, Zhu S, Klug D, Marahiel MA (2013) Lasso peptides from proteobacteria: genome mining employing heterologous expression and mass spectrometry. Biopolymers 100:527–542

    PubMed  Google Scholar 

  22. Ishida K, Lincke T, Behnken S, Hertweck C (2010) Induced biosynthesis of cryptic polyketide metabolites in a Burkholderia thailandensis quorum sensing mutant. J Am Chem Soc 132:13966–13968

    Article  CAS  PubMed  Google Scholar 

  23. Ishida K, Lincke T, Hertweck C (2012) Assembly and absolute configuration of short-lived polyketides from Burkholderia thailandensis. Angew Chem Int Ed 51:5470–5474

    Article  CAS  Google Scholar 

  24. Jain A, Liu X, Wordinger RJ, Yorio T, Cheng Y-Q, Clark AF (2013) Effects of thailanstatins on glucocorticoid response in trabecular meshwork and steroid-induced glaucoma. Invest Ophthalmol Vis Sci 54:3137–3142

    Article  CAS  PubMed  Google Scholar 

  25. Knappe T, Linne U, Zirah S, Rebuffat S, Xie XL, Marahiel M (2008) Isolation and structural characterization of capistruin, a lasso peptide predicted from the genome sequence of Burkholderia thailandensis E264. J Pept Sci 14:97

    Article  Google Scholar 

  26. Knappe TA, Linne U, Robbel L, Marahiel MA (2009) Insights into the biosynthesis and stability of the lasso peptide capistruin. Chem Biol 16:1290–1298

    Article  CAS  PubMed  Google Scholar 

  27. Kumar N, Goldminz AM, Kim N, Gottlieb AB (2013) Phosphodiesterase 4-targeted treatments for autoimmune diseases. BMC Med 11:96

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Lazar Adler NR, Govan B, Cullinane M, Harper M, Adler B, Boyce JD (2009) The molecular and cellular basis of pathogenesis in melioidosis: how does Burkholderia pseudomallei cause disease? FEMS Microbiol Rev 33:1079–1099

    Article  PubMed  Google Scholar 

  29. Lee IK, Yun BS, Cho SM, Kim WG, Kim JP, Ryoo IJ, Koshino H, Yoo ID (1996) Betulinans A and B, two benzoquinone compounds from Lenzites betulina. J Nat Prod 59:1090–1092

    Article  CAS  PubMed  Google Scholar 

  30. Liu X, Biswas S, Berg MG, Antapli CM, Xie F, Wang Q, Tang MC, Tang GL, Zhang L, Dreyfuss G, Cheng Y-Q (2013) Genomics-guided discovery of thailanstatins A, B, and C As pre-mRNA splicing inhibitors and antiproliferative agents from Burkholderia thailandensis MSMB43. J Nat Prod 76:685–693

    Article  CAS  PubMed  Google Scholar 

  31. Mahenthiralingam E, Urban TA, Goldberg JB (2005) The multifarious, multireplicon Burkholderia cepacia complex. Nat Rev Microbiol 3:144–156

    Article  CAS  PubMed  Google Scholar 

  32. Maksimov MO, Pan SJ, James Link A (2012) Lasso peptides: structure, function, biosynthesis, and engineering. Nat Prod Rep 29:996–1006

    Article  CAS  PubMed  Google Scholar 

  33. Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P, Fischbach MA, Weber T, Takano E, Breitling R (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Michalski JM, Golden G, Ikari J, Rennard SI (2012) PDE4: a novel target in the treatment of chronic obstructive pulmonary disease. Clin Pharmacol Ther 91:134–142

    Article  CAS  PubMed  Google Scholar 

  35. Minowa Y, Araki M, Kanehisa M (2007) Comprehensive analysis of distinctive polyketide and nonribosomal peptide structural motifs encoded in microbial genomes. J Mol Biol 368:1500–1517

    Article  CAS  PubMed  Google Scholar 

  36. Nakagawa F, Enokita R, Naito A, Iijima Y, Yamazaki M (1984) Terferol, an inhibitor of cyclic adenosine 3’,5’-monophosphate phosphodiesterase. I. Isolation and characterization. J Antibiot (Tokyo) 37:6–9

    Article  CAS  Google Scholar 

  37. Nakagawa F, Takahashi S, Naito A, Sato S, Iwabuchi S, Tamura C (1984) Terferol, an inhibitor of cyclic adenosine 3’,5’-monophosphate phosphodiesterase. II. Structural elucidation. J Antibiot (Tokyo) 37:10–12

    Article  CAS  Google Scholar 

  38. Nakajima H, Hori Y, Terano H, Okuhara M, Manda T, Matsumoto S, Shimomura K (1996) New antitumor substances, FR901463, FR901464 and FR901465. II. Activities against experimental tumors in mice and mechanism of action. J Antibiot (Tokyo) 49:1204–1211

    Article  CAS  Google Scholar 

  39. Nakajima H, Sato B, Fujita T, Takase S, Terano H, Okuhara M (1996) New antitumor substances, FR901463, FR901464 and FR901465. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. J Antibiot (Tokyo) 49:1196–1203

    Article  CAS  Google Scholar 

  40. Nakajima H, Takase S, Terano H, Tanaka H (1997) New antitumor substances, FR901463, FR901464 and FR901465. III. Structures of FR901463, FR901464 and FR901465. J Antibiot (Tokyo) 50:96–99

    Article  CAS  Google Scholar 

  41. Nguyen T, Ishida K, Jenke-Kodama H, Dittmann E, Gurgui C, Hochmuth T, Taudien S, Platzer M, Hertweck C, Piel J (2008) Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol 26:225–233

    Article  CAS  PubMed  Google Scholar 

  42. Niklison Chirou M, Bellomio A, Dupuy F, Arcuri B, Minahk C, Morero R (2008) Microcin J25 induces the opening of the mitochondrial transition pore and cytochrome c release through superoxide generation. FEBS J 275:4088–4096

    Article  PubMed  Google Scholar 

  43. Page CP, Spina D (2012) Selective PDE inhibitors as novel treatments for respiratory diseases. Curr Opin Pharmacol 12:275–286

    Article  CAS  PubMed  Google Scholar 

  44. Parke JL, Gurian-Sherman D (2001) Diversity of the Burkholderia cepacia complex and implications for risk assessment of biological control strains. Annu Rev Phytopathol 39:225–258

    Article  CAS  PubMed  Google Scholar 

  45. Pavlova O, Mukhopadhyay J, Sineva E, Ebright RH, Severinov K (2008) Systematic structure-activity analysis of microcin J25. J Biol Chem 283:25589–25595

    Article  CAS  PubMed  Google Scholar 

  46. Potharla VY, Wesener SR, Cheng Y-Q (2011) New insights into the genetic organization of the FK228 biosynthetic gene cluster in Chromobacterium violaceum no. 968. Appl Environ Microbiol 77:1508–1511

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Rebuffat S, Blond A, Destoumieux-Garzon D, Goulard C, Peduzzi J (2004) Microcin J25, from the macrocyclic to the lasso structure: implications for biosynthetic, evolutionary and biotechnological perspectives. Curr Protein Pept Sci 5:383–391

    Article  CAS  PubMed  Google Scholar 

  48. Rosengren KJ, Clark RJ, Daly NL, Goransson U, Jones A, Craik DJ (2003) Microcin J25 has a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone. J Am Chem Soc 125:12464–12474

    Article  CAS  PubMed  Google Scholar 

  49. Salomon RA, Farias RN (1992) Microcin 25, a novel antimicrobial peptide produced by Escherichia coli. J Bacteriol 174:7428–7435

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Seyedsayamdost MR, Chandler JR, Blodgett JA, Lima PS, Duerkop BA, Oinuma K, Greenberg EP, Clardy J (2010) Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264. Org Lett 12:716–719

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  51. Taegtmeyer AB, Leuppi JD, Kullak-Ublick GA (2012) Roflumilast–a phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD. Swiss Med Wkly 142:w13628

    PubMed  Google Scholar 

  52. Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M (1994) FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. J Antibiot (Tokyo) 47:301–310

    Article  CAS  Google Scholar 

  53. Ueda H, Nakajima H, Hori Y, Goto T, Okuhara M (1994) Action of FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum no. 968, on Ha-ras transformed NIH3T3 cells. Biosci Biotechnol Biochem 58:1579–1583

    Article  CAS  PubMed  Google Scholar 

  54. Ussery DW, Kiil K, Lagesen K, Sicheritz-Ponten T, Bohlin J, Wassenaar TM (2009) The genus Burkholderia: analysis of 56 genomic sequences. Genome Dyn 6:140–157

    Article  CAS  PubMed  Google Scholar 

  55. Van Lanen SG, Shen B (2006) Microbial genomics for the improvement of natural product discovery. Curr Opin Microbiol 9:252–260

    Article  PubMed  Google Scholar 

  56. VanderMolen KM, McCulloch W, Pearce CJ, Oberlies NH (2011) Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma. J Antibiot (Tokyo) 64:525–531

    Article  CAS  Google Scholar 

  57. Vincent PA, Delgado MA, Farias RN, Salomon RA (2004) Inhibition of Salmonella enterica serovars by microcin J25. FEMS Microbiol Lett 236:103–107

    Article  CAS  PubMed  Google Scholar 

  58. Wang C, Flemming CJ, Cheng Y-Q (2012) Discovery and activity profiling of thailandepsins A through F, potent histone deacetylase inhibitors, from Burkholderia thailandensis E264. Med Chem Comm 3:976–981

    Article  CAS  Google Scholar 

  59. Wang C, Henkes LM, Doughty LB, He M, Wang D, Meyer-Almes FJ, Cheng Y-Q (2011) Thailandepsins: bacterial products with potent histone deacetylase inhibitory activities and broad-spectrum antiproliferative activities. J Nat Prod 74:2031–2038

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Wesener SR, Potharla VY, Cheng Y-Q (2011) Reconstitution of the FK228 biosynthetic pathway reveals cross talk between modular polyketide synthases and fatty acid synthase. Appl Environ Microbiol 77:1501–1507

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Yang LP (2011) Romidepsin: in the treatment of T-cell lymphoma. Drugs 71:1469–1480

    Article  CAS  PubMed  Google Scholar 

  62. Zhang F, He HY, Tang MC, Tang YM, Zhou Q, Tang GL (2011) Cloning and elucidation of the FR901464 gene cluster revealing a complex acyltransferase-less polyketide synthase using glycerate as starter units. J Am Chem Soc 133:2452–2462

    Article  CAS  PubMed  Google Scholar 

  63. Zotchev SB, Sekurova ON, Katz L (2012) Genome-based bioprospecting of microbes for new therapeutics. Curr Opin Biotechnol 23:941–947

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Natural product discovery research in our laboratory has been supported by grants from the US National Institute of Health (R03AI073498 and R01CA152212), a pilot grant from the Lynde and Harry Bradley Foundation, and institutional supports from the University of Wisconsin–Milwaukee and now the University of North Texas Health Science Center.

Author information

Authors and Affiliations

  1. UNT System College of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA

    Xiangyang Liu & Yi-Qiang Cheng

Authors
  1. Xiangyang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yi-Qiang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yi-Qiang Cheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, X., Cheng, YQ. Genome-guided discovery of diverse natural products from Burkholderia sp.. J Ind Microbiol Biotechnol 41, 275–284 (2014). https://doi.org/10.1007/s10295-013-1376-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-013-1376-1

Keywords

Search

Navigation