An ABC transporter encoding gene lndW confers resistance to landomycin E.
Streptomyces globisporus 1912 produces a polyketide antibiotic landomycin E (LaE), which possesses anticancer activity. A 1.8 kb DNA fragment at the end of landomycin E biosynthetic gene cluster was sequenced. DNA sequence analysis of this fragment identified one complete open reading frame, designated lndW. The deduced sequence of lndW gene product revealed significant similarity to the ATP-binding domains of the ABC (ATP-binding protein cassette) superfamily of transport-related proteins. Knockout of lndW had no significant effect on resistance to LaE and its production. The expression of lndW in S. globisporus 1912 was proven via transcriptional fusion of lndW promoter to EGFP (enhanced green fluorescent protein). Overexpression of lndW in S. lividans TK24 conferred resistance to LaE. The mechanism of lndW function in LaE biosynthesis is discussed.
Ostash
Iryna
I
Department of Genetics and Biotechnology, Ivan Franko National University of L'viv, Grushevskogo st.4, L'viv, 79005, Ukraine.
Rebets
Yuriy
Y
Ostash
Bohdan
B
Kobylyanskyy
Anton
A
Myronovskyy
Maksym
M
Nakamura
Tatsunosuke
T
Walker
Suzanne
S
Fedorenko
Victor
V
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000617:Aminoglycosides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D015870:Gene Expression; D005798:Genes, Bacterial; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D010957:Plasmids; D017422:Sequence Analysis, DNA; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics*
D018528:ATP-Binding Cassette Transporters; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C113593:landomycin E