Skip to main content
SpringerLink
Log in

Horizontal gene transfer and gene conversion drive evolution of modular polyketide synthases

  • Genetics and Molecular Biology of Industrial Organisms
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Soil bacteria live in a very competitive environment and produce many secondary metabolites; there appears to be strong selective pressure for evolution of new compounds. Secondary metabolites are the most important source of chemical structures for the pharmaceutical industry and an understanding of the evolutionary process should help in finding novel chemical entities. Modular polyketide synthases are a particularly interesting case for evolutionary studies, because much of the chemical structure can be predicted from DNA sequence. Previous evolutionary studies have concentrated on individual modules or domains and were not able to study the evolution of orthologues. This study overcame this problem by considering complete clusters as “organisms”, so that orthologous modules and domains could be identified and used to characterise evolutionary pathways. Seventeen modular polyketide synthase clusters were identified that fell into six classes. Gene conversion within clusters was very common (affecting about 15 % of domains) and was detected by discordance in phylogenetic trees. An evolutionary model is proposed in which a single cross over between two different clusters (i.e. horizontal gene transfer) would generate a cluster of very different architecture with radically different chemical products; subsequent gene conversion and deletions would explore chemical variants. Two probable examples of such recombination were found. This model suggests strategies for detecting horizontal gene transfer in cluster evolution.

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

Similar content being viewed by others

References

  1. Castonguay R, He W, Chen AY, Khosla C, Cane DE (2007) Stereospecificity of ketoreductase domains of the 6-deoxyerythronolide B synthase. J Am Chem Soc 129:13758–13769. doi:10.1021/ja0753290

    Article  PubMed  CAS  Google Scholar 

  2. Demain AL (2009) Antibiotics: natural products essential to human health. Med Res Rev 29:821–842. doi:10.1002/med.20154

    Article  PubMed  CAS  Google Scholar 

  3. Egan S, Wiener P, Kallifidas D, Wellington EM (2001) Phylogeny of Streptomyces species and evidence for horizontal transfer of entire and partial antibiotic gene clusters. Antonie Van Leeuwenhoek 79:127–133. doi:10.1023/A:1010296220929

    Article  PubMed  CAS  Google Scholar 

  4. Fischbach MA, Walsh CT (2006) Assembly-line enzymology for polyketide and nonribosomal peptide antibiotics: logic, machinery, and mechanisms. Chem Rev 106:3468–3496. doi:10.1021/cr0503097

    Article  PubMed  CAS  Google Scholar 

  5. Fischbach MA, Walsh CT, Clardy J (2008) The evolution of gene collectives: how natural selection drives chemical innovation. Proc Natl Acad Sci U S A 105:4601–4608. doi:10.1073/pnas.0709132105

    Article  PubMed  CAS  Google Scholar 

  6. Hopwood DA (2006) Soil to genomics: the Streptomyces chromosome. Annu Rev Genet 40:1–23. doi:10.1146/annurev.genet.40.110405.090639

    Article  PubMed  CAS  Google Scholar 

  7. Hranueli D, Cullum J, Basrak B, Goldstein P, Long PF (2005) Plasticity of the streptomyces genome-evolution and engineering of new antibiotics. Curr Med Chem 12:1697–1704. doi:10.2174/0929867054367176

    Article  PubMed  CAS  Google Scholar 

  8. Jenke-Kodama H, Börner T, Dittmann E (2006) Natural biocombinatorics in the polyketide synthase genes of the actinobacterium Streptomyces avermitilis. PLoS Comput Biol 2:e132. doi:10.1371/journal.pcbi.0020132

    Article  PubMed  Google Scholar 

  9. Jenke-Kodama H, Sandmann A, Müller R, Dittmann E (2005) Evolutionary implications of bacterial polyketide synthases. Mol Biol Evol 22:2027–2039. doi:10.1093/molbev/msi193

    Article  PubMed  CAS  Google Scholar 

  10. Jones DT, Taylor WR, Thornton JM (1992) The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 8:275–282. doi:10.1093/bioinformatics/8.3.275

    PubMed  CAS  Google Scholar 

  11. Jørgensen H, Fjaervik E, Hakvåg S, Bruheim P, Bredholt H, Klinkenberg G, Ellingsen TE, Zotchev SB (2009) Candicidin biosynthesis gene cluster is widely distributed among Streptomyces spp. isolated from the sediments and the neuston layer of the Trondheim fjord, Norway. Appl Environ Microbiol 75:3296–3303. doi:10.1128/AEM.02730-08

    Article  PubMed  Google Scholar 

  12. Keatinge-Clay AT (2007) A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem Biol 14:898–908. doi:10.1016/j.chembiol.2007.07.009

    Article  PubMed  CAS  Google Scholar 

  13. Keatinge-Clay AT, Stroud RM (2006) The structure of a ketoreductase determines the organization of the β-carbon processing enzymes of modular polyketide synthases. Structure (Lond) 14:737–748. doi:10.1016/j.str.2006.01.009

    Article  CAS  Google Scholar 

  14. Nei M, Kumar S (2000) Molecular evolution and phylogenetics. Oxford University Press, New York

    Google Scholar 

  15. Pandza S, Biuković G, Paravić A, Dadbin A, Cullum J, Hranueli D (1998) Recombination between the linear plasmid pPZG101 and the linear chromosome of Streptomyces rimosus can lead to exchange of ends. Mol Microbiol 28:1165–1176. doi:10.1046/j.1365-2958.1998.00877.x

    Article  PubMed  CAS  Google Scholar 

  16. Poptsova M (2009) Testing phylogenetic methods to identify horizontal gene transfer. Methods Mol Biol 532:227–240. doi:10.1007/978-1-60327-853-9_13

    Article  PubMed  CAS  Google Scholar 

  17. Ridley CP, Lee HY, Khosla C (2008) Evolution of polyketide synthases in bacteria. Proc Natl Acad Sci U S A 105:4595–4600. doi:10.1073/pnas.0710107105

    Article  PubMed  CAS  Google Scholar 

  18. Schmidt HA, Strimmer K, Vingron M, von Haeseler A (2002) TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 18:502–504. doi:10.1093/bioinformatics/18.3.502

    Article  PubMed  CAS  Google Scholar 

  19. Starcevic A, Diminic J, Zucko J, Elbekali M, Schlosser T, Lisfi M, Vukelic A, Long PF, Hranueli D, Cullum J (2011) A novel docking domain interface model that can predict recombination between homoeologous modular biosynthetic gene clusters. J Ind Microbiol Biotechnol 38:1295–1304. doi:10.1007/s10295-010-0909-0

    Article  PubMed  CAS  Google Scholar 

  20. Starcevic A, Jaspars M, Cullum J, Hranueli D, Long PF (2007) Predicting the nature and timing of epimerisation on a modular polyketide synthase. ChemBioChem 8:28–31. doi:10.1002/cbic.200600399

    Article  PubMed  CAS  Google Scholar 

  21. Starcevic A, Zucko J, Simunkovic J, Long PF, Cullum J, Hranueli D (2008) ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures. Nucleic Acids Res 36:6882–6892. doi:10.1093/nar/gkn685

    Article  PubMed  CAS  Google Scholar 

  22. Strimmer K, Goldman N, von Haeseler A (1997) Bayesian probabilities and quartet puzzling. Mol Biol Evol 14:210–213

    Article  CAS  Google Scholar 

  23. Strimmer K, von Haeseler A (1996) Quartet puzzling: a quartet maximum–likelihood method for reconstructing tree topologies. Mol Biol Evol 13:964–969

    Article  CAS  Google Scholar 

  24. Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: molecular evolutionary genetics analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599. doi:10.1093/molbev/msm092

    Article  PubMed  CAS  Google Scholar 

  25. Tamura K, Nei M (1993) Estimation of the number of nucleotide substitutions in the control region of mitochondrial DNA in humans and chimpanzees. Mol Biol Evol 10:512–526

    PubMed  CAS  Google Scholar 

  26. Whelan S, Goldman N (2001) A general empirical model of protein evolution derived from multiple protein families using a maximum likelihood approach. Mol Biol Evol 18:691–699

    Article  PubMed  CAS  Google Scholar 

  27. Yamasaki M, Kinashi H (2004) Two chimeric chromosomes of Streptomyces coelicolor A3(2) generated by single crossover of the wild-type chromosome and linear plasmid SCP1. J Bacteriol 186:6553–6559. doi:10.1128/JB.186.19.6553-6559.2004

    Article  PubMed  CAS  Google Scholar 

  28. Zucko J, Cullum J, Hranueli D, Long PF (2011) Evolutionary dynamics of modular polyketide synthases, with implications for protein design and engineering. J Antibiot 64:89–92. doi:10.1038/ja.2010.141

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by a cooperation grant of the German Academic Exchange Service (DAAD) and the Ministry of Science, Education and Sports, Republic of Croatia (to J.C. and D.H.) and by the grant 058-0000000-3475 (to D.H.) from the Ministry of Science, Education and Sports, Republic of Croatia.

Author information

Authors and Affiliations

  1. Department of Genetics, University of Kaiserslautern, Postfach 3049, 67653, Kaiserslautern, Germany

    Jurica Zucko & John Cullum

  2. Department of Chemistry, Institute of Pharmaceutical Science, King’s College London, Franklin–Wilkins Building, Stamford Street, London, SE1 9NH, UK

    Paul F. Long

  3. Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000, Zagreb, Croatia

    Jurica Zucko & Daslav Hranueli

Authors
  1. Jurica Zucko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul F. Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daslav Hranueli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John Cullum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John Cullum.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zucko, J., Long, P.F., Hranueli, D. et al. Horizontal gene transfer and gene conversion drive evolution of modular polyketide synthases. J Ind Microbiol Biotechnol 39, 1541–1547 (2012). https://doi.org/10.1007/s10295-012-1149-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10295-012-1149-2

Keywords

Search

Navigation