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Biosynthetic gene cluster of the glycopeptide antibiotic teicoplanin: characterization of two glycosyltransferases and the key acyltransferase.
The product of another ORF, orf11*, was demonstrated in vitro to transfer n-acetyl-, n-butyryl-, and n-octanoyl-groups from acyl-CoA donors either to a free UDP-aminosugar or to an aminosugar moiety in the teicoplanin pseudoaglycone, thus identifying Orf11* as the key acyltransferase in teic Starship maturation. Expand
Crystal structure and mechanism of a bacterial fluorinating enzyme
The sequence and three-dimensional structure of the first native fluorination enzyme, 5′-fluoro-5′-deoxyadenosine synthase, from Streptomyces cattleya is reported, and a nucleophilic substitution mechanism for this biological fluorination reaction is proposed. Expand
The gene cluster for fluorometabolite biosynthesis in Streptomyces cattleya: a thioesterase confers resistance to fluoroacetyl-coenzyme A.
A genomic library of Streptomyces cattleya was screened to isolate a gene cluster encoding enzymes responsible for the production of fluorine-containing metabolites, finding that flK encodes a thioesterase which catalyzes the selective breakdown of fluoroacetyl- CoA but not acetyl-CoA, suggesting that it provides the producing strain with a mechanism for resistance tofluoroacetate. Expand
Biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics.
The development of biosynthesis knowledge over the past half-century is discussed, with emphasis on the relatively recent contributions of molecular biology to the elucidation of these biosynthetic pathways. Expand
Identification using LC-MSn of co-metabolites in the biosynthesis of the polyketide toxin mycolactone by a clinical isolate of Mycobacterium ulcerans.
LC-MSn analysis of mycolactone toxin from extracts of Mycobacterium ulcerans has shown that minor co-metabolites, including two previously unreported, differ structurally from mycolactone only in aExpand
Directed mutagenesis alters the stereochemistry of catalysis by isolated ketoreductase domains from the erythromycin polyketide synthase.
Modelling of ketoreductase domains showed that conserved amino acids previously correlated with production of alternative alcohol configurations lie in the active site, confirming the role of key residues in stereocontrol and suggesting an additional way to make rational alterations in polyketide antibiotic structure. Expand
Glyceryl‐S‐Acyl Carrier Protein as an Intermediate in the Biosynthesis of Tetronate Antibiotics
It is shown that purified recombinant FkbH‐like protein Tmn16 from the TMN gene cluster catalyses the efficient transfer of a glyceryl moiety from D‐1,3‐bisphosphoglycerate to either of the dedicated ACPs, Tmn7a and ChlD2, to form Glyceryl‐S‐ACP, which directly implicates this compound as an intermediate in tetronate biosynthesis as well. Expand
Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain.
It is reported here that the AHBA side chain of butirosin is transferred from the acyl carrier protein (ACP) BtrI to the parent aminoglycoside ribostamycin as a gamma-glutamylated dipeptide by the ACP:aminoglycosid acyltransferase BtrH. Expand
Elaboration of Neosamine Rings in the Biosynthesis of Neomycin and Butirosin
The product of the btrB gene, a homologue of neo‐18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans, exhibits the same activity as Neo‐18; this indicates that there is a similar reaction sequence in both but irosin and neomycin biosynthesis. Expand