Saccharomonospora azurea SZMC 14600 is a member of the family Pseudonocardiaceae exclusively used for industrial scale production of primycin a large 36-membered non-polyene macrolide lactone antibiotic belonging to the polyketide class of natural products. Even though maximum antibiotic yield has been achieved by empirically optimized two-step fermentation process, little is known about the molecular components and mechanisms underlying the efficient antibiotic production. In order to identify differentially expressed proteins (DEPs) between the pre- and main-fermentation stages of primycin, comparative 2D-PAGE experiments were performed. In total, 98 DEP spots were reproducibly detected, out of which four spots were excised from gels, and identified through MALDI-TOF/TOF mass spectrometry. Peptide mass fingerprint analysis revealed peptide matches to HicB antitoxin for the HicAB toxin-antitoxin system (EHK86651), to a nucleoside diphosphate kinase regulator ((Ndk; EHK81899) and two other proteins with unknown function (EHK88946 and EHK86777).
Bérdy, J. (2005) Bioactive microbial metabolites. J. Antibiot. 58, 1–26.
Butt, A., Higman, V. A., Williams, C., Crump, M. P., Hemsley, C. M., Harmer, N., Titball, R. W. (2014) The HicA toxin from Bulkholderia pseudomallei has role in persister cell formation. Biochem. J. 459, 333–344.
Chakrabarty, A. M. (1998) Nucleoside diphosphate kinase: role inbacterial growth, virulence, cell signalling and polysaccharide synthesis. Mol. Microbiol. 8, 875–882.
Chaudhary, A. K., Dhakal, D., Sohng, J. K. (2013) An insight into the “omics” based engineering of Streptomycetes for secondary metabolite overproduction. Biomed. Res. Int. doi:10.1155/2013/968518
Csepregi, K., Valasek, A., Pénzes, Á., Tóth, Zs., Kiss, É. I., Kerepesi, I., Horváth, B., Nagy, I., Fekete, Cs. (2012) Draft genome sequence of an efficient antibiotic-producing industrial strain of Saccharomonospora azurea, SZMC 14600. J. Bacteriol. 194, 1263.
De Bast, M. S., Mine, N., Van Melderen, L. (2008) Chromosomal toxin-antitoxin systems may act as antiaddiction modules. J. Bacteriol. 190, 4603–4609.
Durand, S., Jahn, N., Condon, C., Brant, S. (2012) Type I. toxin-antitoxin systems in Bacillus subtilis. RNA Biol. 9, 1491–1497.
Feiszt, P., Mestyán, Gy., Kerényi, M., Dobay, O., Szabó, J., Dombrádi, Zs., Urbán, E., Emody, L. (2014) Re-evaluation of in vitro activity of primycin against prevalent multiresistent bacteria. Int. J. Med. Microbiol. 304, 1077–1085.
Goeders, N., Van Melderen, L. (2014) Toxin-antitoxin systems as multilevel interaction systems. Toxins (Basel) 6, 304–324.
Hiller, K., Grote, A., Maneck, M., Münch, R., Jahn, D. (2006) JVirGel 2.0: computational prediction of proteomes separated via two-dimensional gel electrophoresis. Bioinformatics 22, 2441–2443.
Juhász, Á., Pénzes, Á., Péteri, Z., Pallos, J. P., Seffer, V., Feiszt, P., Pesti, M., Fekete, Cs., Vágvölgyi, Cs., Gazdag, Z., Papp, G. Process for producing primycin, primycin component(s), precursors and metabolites thereof via fermentation by the use of bacterial species Saccharomonospora azurea. 5 May 2011, WIPO patent application WO/2011/051741
Magnuson, R. D. (2007) Hypothetical functions of toxin-antitoxin systems. J. Bacteriol. 189, 6089–6092.
Otero, J. M., Nielsen, J. (2010) Industrial systems biology. Biotechnol. Bioeng. 15, 439–460.
Ogura, T., Hiraga, S. (1983) Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc. Natl Acad. Sci. USA. 80, 4784–4788.
Raja, A., Prabakaran, P. (2011) Actinomycetes and drug-an overview. Am. J. Drug Discov. Dev. 1, 75–84.
Shevchenko, A., Tomas, H., Havlis, J., Olsen, J.V., Mann, M. (2006) In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 6, 2856–2860.
Yang, Q., Ding, X., Liu, X., Liu, S., Sun, J., Yu, Z., Hu, S., Rang, J., He, H., He, L., Xia, L. (2014) Differential proteomic profiling reveals regulatory proteins and novel links between primary metabolism and spinosad production in Saccharopolyspora spinosa. Microb. Cell Fact. 13:e27 doi: 10.1186/1475-2859-13-27
Vályi-Nagy, T., Úri, J., Szilágyi, I. (1954) Primycin, a new antibiotic. Nature 174, 1105–1106.
Wang, W., Vignani, R., Scali, M., Cresti, M. (2006) A universal and rapid protocol for protein extraction from recalcitrant plant tissues for proteomic analysis. Electrophoresis 27, 2782–2786.
World Health Organization (WHO) Antimicrobial Resistance Global Report on surveillance (2014)
Wongtrakoongate, P., Mongkoldhumrongkul, N., Kamchonwongpaisan, S. K., Tungpradabkul, S. (2007) Compatative proteomic profiles and potential markers between Bulkholderia pseudomallei and Bulkholderia thailandensis. Mol. Cell. Probes 21, 81–91.