Abstract
A 3 kb DNA fragment from the Streptomyces globisporus 1912 landomycin E (LaE) biosynthetic gene cluster (lnd) was completely sequenced. Three open reading frames were identified, lndGT4, lndZ4, and lndZ5, whose probable translation products resemble a glycosyltransferase, a reductase, and a hydroxylase, respectively. Studies of generated mutants from disruption and complementation experiments involving the lndGT4 gene allowed us to determine that LndGT4 controls the terminal L-rhodinose sugar attachment during LaE biosynthesis and that LndZ4/LndZ5 are responsible for the unique C11-hydroxylation of the landomycins. Generation of the novel landomycins F, G, and H in the course of these studies provided evidence for the flexibility of lnd glycosyltransferases toward their acceptor substrates and a basis for initial structure-activity relationships within the landomycin family of antibiotics.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aminoglycosides / biosynthesis*
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Aminoglycosides / chemistry*
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Aminoglycosides / pharmacology
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Division / drug effects
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Cell Line, Tumor
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Glycosyltransferases / analysis
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Glycosyltransferases / genetics*
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Glycosyltransferases / metabolism
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Humans
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Mixed Function Oxygenases / analysis
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Mixed Function Oxygenases / genetics
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Mixed Function Oxygenases / metabolism
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Molecular Sequence Data
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Multigene Family
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Mutation
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Oxidoreductases / analysis
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Oxidoreductases / genetics
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Oxidoreductases / metabolism
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Streptomyces / enzymology
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Streptomyces / genetics*
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Streptomyces / metabolism
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Structure-Activity Relationship
Substances
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Aminoglycosides
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Antineoplastic Agents
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landomycin D
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landomycin E
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landomycin F
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landomycin G
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landomycin H
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Mixed Function Oxygenases
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Oxidoreductases
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Glycosyltransferases
Associated data
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GENBANK/AY443343
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GENBANK/AY443344
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GENBANK/AY443345
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GENBANK/AY523868
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GENBANK/AY528820