An influence of the copy number of biosynthetic gene clusters on the production level of antibiotics in a heterologous host.
Streptomyces albus J1074 is a well-known host for heterologous expression of secondary metabolites. To further increase its potential and to study the influence of cluster multiplication, additional φC31-attachment site was integrated into its genome using a system for transposon mutagenesis. Four secondary metabolite clusters were expressed in strains with different numbers of attachment sites, ranging from one to three copies of the site. Secondary metabolite production was examined and a new compound could be detected, purified and its structure was elucidated.
Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, Saarbrücken 66123, Germany.
Niko
N
Manderscheid
PharmBioTec GmbH, Science Park 1, 66123 Saarbrücken, Germany.
Bohdan
B
Bilyk
Microbial Genomics and Biotechnology, Center for Biotechnology (CeBiTec), Universität Bielefeld, Sequenz 1, 33615 Bielefeld, Germany.
Tobias
T
Busche
Microbial Genomics and Biotechnology, Center for Biotechnology (CeBiTec), Universität Bielefeld, Sequenz 1, 33615 Bielefeld, Germany.
Jörn
J
Kalinowski
Universität Siegen, Fakultät IV, Organische Chemie II, Adolf-Reichwein-Str. 2, 57076 Siegen, Germany.
Thomas
T
Paululat
University of Freiburg, Institute for Pharmaceutical Sciences, Stefan-Meier str.14, 79104 Freiburg, Germany.
Andreas
A
Bechthold
BASF SE, 67056 Ludwigshafen, Germany.
Lutz
L
Petzke
Helmholtz-Institute for Pharmaceutical Research Saarland, Saarland University, Campus C2.3, Saarbrücken 66123, Germany; Department of Pharmaceuticla Biotechnology, Universität des Saarlandes, Campus Geb. C2.3, 66123 Saarbrücken, Germany. Electronic address: andriy.luzhetskyy@helmholtz-hzi.de.
Andriy
A
Luzhetskyy
D000900:Anti-Bacterial Agents / Q000032:analysis / Q000378:metabolism*; D018628:Gene Dosage / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*
D000900:Anti-Bacterial Agents
Antibiotic production; Heterologous expression; Multiple attachment sites; Strain development; Streptomyces albus J1074; φC31-encoded recombination system