Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoglycosides / biosynthesis*
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Aminoglycosides / pharmacology
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Antibiotics, Antineoplastic / biosynthesis
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Antibiotics, Antineoplastic / pharmacology
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Disaccharides / biosynthesis*
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Disaccharides / pharmacology
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Gene Targeting*
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Humans
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Inhibitory Concentration 50
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Naphthoquinones / chemistry
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Naphthoquinones / pharmacology
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Oligosaccharides / biosynthesis*
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Oligosaccharides / chemistry
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Oligosaccharides / pharmacology
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Oxygenases / genetics
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Streptomyces / genetics*
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Streptomyces / metabolism
Substances
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Aminoglycosides
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Antibiotics, Antineoplastic
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Disaccharides
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Naphthoquinones
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Oligosaccharides
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landomycin M
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landomycin O
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landomycinone
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Oxygenases