Reconstructing the phylogeny of glycopeptide biosynthetic gene clusters

  • O. S. Yushchuk Ivan Franko National University of Lviv, Ukraine, 79005, Lviv, Hrushevskoho str., 4
  • B. O. Ostash Ivan Franko National University of Lviv, Ukraine, 79005, Lviv, Hrushevskoho str., 4
  • L. O. Horbal Helmholtz-Institute for Pharmaceutical Research Saarland, Germany, Saarbrucken
  • V. O. Fedorenko Ivan Franko National University of Lviv, Ukraine, 79005, Lviv, Hrushevskoho str., 4


Aim. In current study we have endeavored to analyze the phylogeny of 18 sequenced glycopeptide biosynthetic gene clusters. Methods. Standard methods of phylogenetic reconstruction were used in this research. Results. We have created sets of conservative genes, present in all selected clusters and analyzed their phylogeny. In most cases two main clades were formed on final trees. One clade always included genes from biosynthetic clusters of teicoplanin-like compounds, the second – genes from biosynthetic clusters of vancomycin-like compounds. Finally, we have built a multilocus phylogeny (MLP) of selected clusters. Once again, two groups of glycopeptide gene clusters could be recognized according to the results of MLP: biosynthetic clusters of teicoplanin-like compounds and biosynthetic clusters of vancomycin-like compounds. These groups do not correlate with accepted structural classification of glycopeptides. Biosynthetic cluster of unusual antibiotic feglymycin appeared to be closely related to biosynthetic clusters of teicoplanin-like compounds. Conclusions. Based on the obtained results we proposed a possible scenario of the evolution of glycopeptide biosynthetic gene clusters.
Keywords: gene cluster, glycopeptide antibiotic, phylogeny.


Binda E., Marinelli F., Marcone G.L. Old and new glycopeptide antibiotics: action and resistance. Antibiotics (Basel). 2014. V. 3 (4). P. 572-594. doi: 10.3390/antibiotics3040572

Medema M., Cimermancic P., Sali A., Takano E., Fischbach M.A. A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis. PLoS Comput. Biol. 2014. V. 10 (12). P. 1-12. doi: 10.1371/journal.pcbi.1004016

Spohn M., Kirchner N., Kulik A., Jochim A., Wolf F., Muenzer P., Borst O., Gross H., Wohlleben W., Stegmann E. Overproduction of Ristomycin A by activation of a silent gene cluster in A. japonicum MG417-CF17. Antimicrob. Ag. Chemother. 2014. V. 58 (10). P. 6185-6196. doi: 10.1128/AAC.03512-14

Donadio S., Sosio M., Stegmann E., Weber T., Wohlleben W. Comparative analysis and insights into the evolution of gene clusters for glycopeptide antibiotic biosynthesis. Mol. Genet. Genomics. 2005. V. 274 (1). P. 40-50. doi: 10.1007/s00438-005-1156-3

Kearse M., Moir R., Wilson A., Stones-Havas S., Cheung M., Sturrock S., Buxton S., Cooper A., Markowitz S., Duran C., Thierer T., Ashton B., Meintjes P., Drummond A. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics. 2012. V. 28 (12). P. 1647-1649. doi: 10.1093/bioinformatics/bts199

Tamura K., Stecher G., Peterson D., Filipski A., Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol. Biol. Evol. 2013. V. 30 (12). P. 2725-2729. doi: 10.1093/molbev/mst197

Shawky R., Puk O., Wietzorrek A., Pelzer S., Takano E., Wohlleben W., Stegmann E. The border sequence of the balhimycin biosynthesis gene cluster from A. balhimycina contains bbr, encoding a StrR-like pathway-specific regulator. J. Mol. Microbiol. Biotechnol. 2007. V. 13 (1-3). P. 76-88. doi: 10.1159/000103599

Horbal L., Kobylyanskyy A., Truman A.W., Zaburranyi N., Ostash B., Luzhetskyy A., Marinelli F., Fedorenko V. The pathway-specific regulatory genes, tei15* and tei16*, are the master switches of teicoplanin production in A. teichomyceticus. Appl. Microbiol. Biotechnol. 2014. V. 98 (22). P. 9295-9309. doi: 10.1007/s00253-014-5969-z

Lo Grasso L., Maffioli S., Sosio M., Bibb M., Puglia A.M., Alduina R. Two master switch regulators trigger A40926 biosynthesis in Nonomuraea sp. strain ATCC 39727. J. Bacteriol. 2015. V. 197 (15). P. 2536-2544. doi: 10.1128/JB.00262-15

Thykaer J., Nielsen J., Wohlleben W., Weber T., Gutknecht M., Lantz A.E., Stegmann E. Increased glycopeptide production after overexpression of shikimate pathway genes being part of the balhimycin biosynthetic gene cluster. Metab. Eng. 2010. V. 12 (5). P. 455-461. doi: 10.1016/j.ymben.2010.05.001

Bischoff D., Bister B., Bertazzo M., Pfeifer V., Stegmann E., Nicholson GJ., Keller S., Pelzer S., Wohlleben W., Süssmuth R.D. The biosynthesis of vancomycin-type glycopeptide antibiotics - a model for oxidative side-chain cross-linking by oxygenases coupled to the action of peptide synthetases. Chembiochem. 2005. V. 6 (2). P. 267-272. doi: 10.1002/cbic.200400328

Nicolaou K., Boddy C.N., Bräse S., Winssinger N. Chemistry, Biology, and Medicine of the Glycopeptide Antibiotics. Angew. Chem. Int. Ed. Engl. 1999. V. 38 (15). P. 2096-2152. doi: 10.1002/(SICI)1521-3773(19990802)38:15<2096::AID-ANIE2096>3.0.CO;2-F