Generation of novel landomycins M and O through targeted gene disruption.
Two genes from Streptomyces cyanogenous S136 that encode the reductase LanZ4 and the hydroxylase LanZ5, which are involved in landomycin A biosynthesis, were characterized by targeted gene inactivation. Analyses of the corresponding mutants as well as complementation experiments have allowed us to show that LanZ4 and LanZ5 are responsible for the unique C-11-hydroxylation that occurs during landomycin biosynthesis. Compounds accumulated by the lanZ4/Z5 mutants are the previously described landomycin F and the new landomycins M and O.
Luzhetskyy
Andriy
A
Institut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität, Stefan-Meier-Strasse 19, 79104 Freiburg, Germany.
Zhu
Lili
L
Gibson
Miranda
M
Fedoryshyn
Marta
M
Dürr
Clemens
C
Hofmann
Carsten
C
Hoffmeister
Dirk
D
Ostash
Bohdan
B
Mattingly
Cynthia
C
Adams
Val
V
Fedorenko
Victor
V
Rohr
Jürgen
J
Bechthold
Andreas
A
D000617:Aminoglycosides / Q000096:biosynthesis* / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004187:Disaccharides / Q000096:biosynthesis* / Q000494:pharmacology; D018390:Gene Targeting; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology; D009844:Oligosaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D010105:Oxygenases / Q000235:genetics; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D004187:Disaccharides; D009285:Naphthoquinones; D009844:Oligosaccharides; C503607:landomycin M; C503608:landomycin O; C490011:landomycinone; D010105:Oxygenases