Novobiocin biosynthesis in<i>Streptomyces spheroides</i>: identification of a dimethylallyl diphosphate:4-hydroxyphenylpyruvate dimethylallyl transferase

Steffensky, Marion; Li, Shu-Ming; Vogler, Bernhard; Heide, Lutz

doi:10.1111/j.1574-6968.1998.tb12930.x

Cited by 18 publications

(6 citation statements)

References 26 publications

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“…The amino acid sequences of Ptf At , Ptf Ss , and Ptf Bf , as well as those of the gene products of ptf Pm and ptf Mc , are closely related to the bacterial enzymes NovQ and CloQ, which catalyze the 3-prenylation of 4-hydroxyphenylpyruvate in the biosynthesis of clorobiocin and novobiocin (2,24,33). The protein encoded by ptf Mc has therefore been annotated as "NovQ" (GenBank TM accession number EEQ32241).…”

Section: Discussionmentioning

confidence: 99%

A New Group of Aromatic Prenyltransferases in Fungi, Catalyzing a 2,7-Dihydroxynaphthalene 3-Dimethylallyl-transferase Reaction

Haug-Schifferdecker

Arican

Brückner

et al. 2010

Journal of Biological Chemistry

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Five fungal genomes from the Ascomycota (sac fungi) were found to contain a gene with sequence similarity to a recently discovered small group of bacterial prenyltransferases that catalyze the C-prenylation of aromatic substrates in secondary metabolism. The genes from Aspergillus terreus NIH2624, Botryotinia fuckeliana B05.10 and Sclerotinia sclerotiorum 1980 were expressed in Escherichia coli, and the resulting His 8 -tagged proteins were purified and investigated biochemically. Their substrate specificity was found to be different from that of any other prenyltransferase investigated previously. Using 2,7-dihydroxynaphthalene (2,7-DHN) and dimethylallyl diphosphate as substrates, they catalyzed a regiospecific Recently, a new family of prenyltransferases has been discovered in bacteria of the genus Streptomyces (1-4). They are involved in the biosynthesis of secondary metabolites, e.g. antibiotics. The members of this family are characterized by a new protein fold, termed PT barrel (1). The PT barrel consists of five repetitive ␣␣␤␤ elements, with the ␤ strands forming a central barrel. In contrast to the TIM barrel, the PT barrel consists of 10 antiparallel ␤ strands and contains the active site of the enzyme in its spacious lumen. The members of this enzyme family catalyze Friedel-Crafts alkylations of aromatic substrates, i.e. the formation of carbon-carbon-bonds between C-1 or C-3 of the isoprenoid substrate and an aromatic carbon of the acceptor substrate. In contrast to the membrane-bound aromatic prenyltransferases of ubiquinone, menaquinone, and plastoquinone biosynthesis (5), the enzymes containing the PT barrel are soluble proteins and do not contain (N/D)DxxD motifs for binding of the isoprenoid substrate.

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Section: Discussionmentioning

confidence: 99%

A New Group of Aromatic Prenyltransferases in Fungi, Catalyzing a 2,7-Dihydroxynaphthalene 3-Dimethylallyl-transferase Reaction

Haug-Schifferdecker

Arican

Brückner

et al. 2010

Journal of Biological Chemistry

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“…Ring A is attached to the amino group of ring B via an amide bond. Both aromatic rings are derived from tyrosine, ring C is derived from glucose, and the prenyl group of ring A is formed via the nonmevalonate pathway (1)(2)(3). The antimicrobial activity of novobiocin results from its interaction with bacterial DNA gyrase, which has been investigated by x-ray crystallographic studies (4 -7).…”

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Cloning, Overexpression, and Purification of Novobiocic Acid Synthetase from Streptomyces spheroides NCIMB 11891

Steffensky

Heide

2000

Journal of Biological Chemistry

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“…Novobiocin, clorobiocin, and coumermycin A 1 are formed by different Streptomyces strains (2,3). The 3-prenylated 4-hydroxybenzoic acid (4HB) moiety of novobiocin (called ring A) has been shown to be derived from tyrosine and an isoprenoid precursor (4), but conflicting suggestions have been made for the prenylation substrate (5)(6)(7)(8). 3-Prenylated 4HB moieties are known as intermediates in the biosynthesis of ubiquinones (9,10) and shikonin (11), where they are formed from 4HB under catalysis of membrane-bound prenyltransferases.…”

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confidence: 99%

CloQ, a prenyltransferase involved in clorobiocin biosynthesis

Pojer

Wemakor

Kammerer

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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115

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Ring A (3-dimethylallyl-4-hydroxybenzoic acid) is a structural moiety of the aminocoumarin antibiotics novobiocin and clorobiocin. In the present study, the prenyltransferase involved in the biosynthesis of this moiety was identified from the clorobiocin producer (Streptomyces roseochromogenes), overexpressed, and purified. It is a soluble, monomeric 35-kDa protein, encoded by the structural gene cloQ. 4-Hydroxyphenylpyruvate and dimethylallyl diphosphate were identified as the substrates of this enzyme, with K m values determined as 25 and 35 M, respectively. A gene inactivation experiment confirmed that cloQ is essential for ring A biosynthesis. Database searches did not reveal any similarity of CloQ to known prenyltransferases, and the enzyme did not contain the typical prenyl diphosphate binding site (N͞D)DXXD. In contrast to most of the known prenyltransferases, the enzymatic activity was not dependent on the presence of magnesium, and in contrast to the membrane-bound polyprenyltransferases involved in ubiquinone biosynthesis, CloQ did not accept 4-hydroxybenzoic acid as substrate. CloQ and the similar NovQ from the novobiocin producer seem to belong to a new class of prenyltransferases.

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Novobiocin biosynthesis inStreptomyces spheroides: identification of a dimethylallyl diphosphate:4-hydroxyphenylpyruvate dimethylallyl transferase

Cited by 18 publications

References 26 publications

A New Group of Aromatic Prenyltransferases in Fungi, Catalyzing a 2,7-Dihydroxynaphthalene 3-Dimethylallyl-transferase Reaction

A New Group of Aromatic Prenyltransferases in Fungi, Catalyzing a 2,7-Dihydroxynaphthalene 3-Dimethylallyl-transferase Reaction

Cloning, Overexpression, and Purification of Novobiocic Acid Synthetase from Streptomyces spheroides NCIMB 11891

CloQ, a prenyltransferase involved in clorobiocin biosynthesis

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