2000
DOI: 10.1128/aac.44.5.1214-1222.2000
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Identification of the Novobiocin Biosynthetic Gene Cluster of Streptomyces spheroides NCIB 11891

Abstract: The novobiocin biosynthetic gene cluster from Streptomyces spheroides NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes. Doublestranded sequencing of 25.6 kb revealed the presence of 23 putative open reading frames (ORFs), including the gene for novobiocin resistance, gyrB r , and at least 11 further ORFs to which a possible role in novobiocin biosynthesis could be assigned. An insertional inactivation experiment with a dNDP-glucose 4,… Show more

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Cited by 187 publications
(179 citation statements)
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References 60 publications
(45 reference statements)
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“…In vitro biochemical characterization of the encoded gene product demonstrated that 4-hydroxyphenylpyruvate (4-HPP) served as the aromatic acceptor with the C5 isoprenoid diphosphate, DMAPP, serving as the prenyl donor in a divalent cationindependent reaction [14]. Moreover, the closely related NovQ protein found in S. spheroides [15] (84% sequence identity to CloQ) was speculated to participate in the dimethylallylation of Ring A of the structurally related aminocoumarin novobiocin [14].…”
Section: Discovery Of a New Subgroup Of Aromatic Ptasesmentioning
confidence: 99%
See 1 more Smart Citation
“…In vitro biochemical characterization of the encoded gene product demonstrated that 4-hydroxyphenylpyruvate (4-HPP) served as the aromatic acceptor with the C5 isoprenoid diphosphate, DMAPP, serving as the prenyl donor in a divalent cationindependent reaction [14]. Moreover, the closely related NovQ protein found in S. spheroides [15] (84% sequence identity to CloQ) was speculated to participate in the dimethylallylation of Ring A of the structurally related aminocoumarin novobiocin [14].…”
Section: Discovery Of a New Subgroup Of Aromatic Ptasesmentioning
confidence: 99%
“…In vitro biochemical characterization of the encoded gene product demonstrated that 4-hydroxyphenylpyruvate (4-HPP) served as the aromatic acceptor with the C5 isoprenoid diphosphate, DMAPP, serving as the prenyl donor in a divalent cationindependent reaction [14]. Moreover, the closely related NovQ protein found in S. spheroides [15] (84% sequence identity to CloQ) was speculated to participate in the dimethylallylation of Ring A of the structurally related aminocoumarin novobiocin [14].Two years after these initial discoveries, an open reading frame designated orf2 (now renamed nphB) was identified based onits similarityto cloQ/novQ in a gene cluster associated with the biosynthesis of the geranylated natural product naphterpin in Streptomyces sp. strain CL190 [16].…”
mentioning
confidence: 99%
“…Biochemical characterization of the P450s that catalyze the oxidation of carrier protein-bound amino acids in novobiocin and nikkomycin biosynthesis has been performed (23,25). Walsh and co-workers demonstrated that the oxidation of tyrosine to ␤-R-hydroxytyrosine is catalyzed by the P450 NovI, with tyrosine bound to another protein in the novobiocin biosynthetic operon, NovH.…”
mentioning
confidence: 99%
“…The proposed role for NovJ and NovK was first intuited from their location adjacent to noVHI in the noV gene cluster (noVH,I,J,K) (6) and from bioinformatics analysis that indicates that they belong to the nicotinamide-dependent -keto acid reductase superfamily (30). Most intriguingly, we noted homology to a pair of orfs, bbsC and bbsD, the predicted -oxidases in anaerobic toluene catabolism (31).…”
Section: Discussionmentioning
confidence: 73%
“…These studies are enabled by the DNA sequence determinations of the biosynthetic gene clusters for all three of the aminocoumarin antibiotics, novobiocin, clorobiocin, and coumermycin, by the Heide group in Tubingen (6)(7)(8).…”
mentioning
confidence: 99%