A Streptomyces avermitilis gene encoding a 4-hydroxyphenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli

Denoya, Claudio D.; Skinner, Deborah D.; Morgenstern, Margaret R.

doi:10.1128/jb.176.17.5312-5319.1994

Cited by 86 publications

(86 citation statements)

References 47 publications

(40 reference statements)

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“…culture both on solid and liquid media [16,7]. The authors found that the intensity of this pigment could be increased by the addition of L-tyrosine.…”

Section: Hppd Activitymentioning

confidence: 83%

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The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

Lee¹,

Zhang²,

MacKinnon³

et al. 1996

FEBS Letters

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We have cloned and overexpressed rat 4-hydroxyphenylpyruvate dioxygenase (4HPPD) in Escherichia coilThe soluble, active recombinant enzyme was shown to contain both 4HPPD and ¢x-ketoisocaproate dioxygenase (¢zKICD) activity. However, upon truncation of the 14 amino acids at the Cterminus by site-directed mutagenesis, the resulting mutant enzyme (rat F antigen) exhibited complete loss of 4HPPD and ff~KICD activities. This finding suggests that the C-terminal extension domain plays an essential role in the catalytic activity of the enzyme.Key words: 4-Hydroxyphenylpyruvate dioxygenase; c¢-Ketoisocaproate dioxygenase; Rat F antigen; C-terminal domain Database analysis and multiple alignment of amino acid sequences revealed that rat F antigen (RFA) exhibits a high degree of homology (> 90%) with 4HPPD from a variety of species. RFA is a protein of about 43 kDa found predominantly in the hepatic cytoplasm of mammals. First identified in 1968, it has been extensively studied as a model of tolerance but to date, its function is still unknown [10 12].

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“…culture both on solid and liquid media [16,7]. The authors found that the intensity of this pigment could be increased by the addition of L-tyrosine.…”

Section: Hppd Activitymentioning

confidence: 83%

“…The possible role of rat F antigen only came to light when 4HPPD from Streptomyces, human and porcine were cloned [16,18,19]. Sequence comparison showed that RFA bore a striking similarity to 4HPPD isolated from these organisms.…”

Section: Otkicd Activitymentioning

confidence: 99%

The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

Lee¹,

Zhang²,

MacKinnon³

et al. 1996

FEBS Letters

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“…These melanin pigments are produced on solid medium and then later accumulate in the spores. Another melanin is an ochronotic pigment that is derived from homogentiginic acid and produced in both solid and liquid media (18). Two melanin gene clusters involving tyrosinase were found in the genome (Figs.…”

Section: Resultsmentioning

confidence: 99%

Genome sequence of an industrial microorganism Streptomyces avermitilis : Deducing the ability of producing secondary metabolites

Ōmura

Ikeda

Ishikawa

et al. 2001

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

763

524

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Streptomyces avermitilis is a soil bacterium that carries out not only a complex morphological differentiation but also the production of secondary metabolites, one of which, avermectin, is commercially important in human and veterinary medicine. The major interest in this genus Streptomyces is the diversity of its production of secondary metabolites as an industrial microorganism. A major factor in its prominence as a producer of the variety of secondary metabolites is its possession of several metabolic pathways for biosynthesis. Here we report sequence analysis of S. avermitilis, covering 99% of its genome. At least 8.7 million base pairs exist in the linear chromosome; this is the largest bacterial genome sequence, and it provides insights into the intrinsic diversity of the production of the secondary metabolites of Streptomyces. Twenty-five kinds of secondary metabolite gene clusters were found in the genome of S. avermitilis. Four of them are concerned with the biosyntheses of melanin pigments, in which two clusters encode tyrosinase and its cofactor, another two encode an ochronotic pigment derived from homogentiginic acid, and another polyketide-derived melanin. The gene clusters for carotenoid and siderophore biosyntheses are composed of seven and five genes, respectively. There are eight kinds of gene clusters for type-I polyketide compound biosyntheses, and two clusters are involved in the biosyntheses of type-II polyketide-derived compounds. Furthermore, a polyketide synthase that resembles phloroglucinol synthase was detected. Eight clusters are involved in the biosyntheses of peptide compounds that are synthesized by nonribosomal peptide synthetases. These secondary metabolite clusters are widely located in the genome but half of them are near both ends of the genome. The total length of these clusters occupies about 6.4% of the genome.S treptomyces is a genus of Gram-positive bacteria that grows in soil, marshes, and coastal marine habitats and forms filamentous mycelium-like eukaryote fungi. Morphological differentiation in Streptomyces involves the formation of a lawn of aerial hyphae on the colony surface that stands up into the air and differentiates into chains of spores (1). This process, unique among Gram-positive bacteria, requires the specialized coordination of metabolism and is more complex than other Gram-positive bacteria. The most interesting property of Streptomyces is its ability to produce secondary metabolites including antibiotics and bioactive compound (2) value in human and veterinary medicine, agriculture, and unique biochemical tools. Structural diversity is observed in these secondary metabolites that encompass not only antibacterial, antifungal, antiviral, and antitumor compounds, but also metabolites with immunosuppressant, antihypertensive, and antihypercholesterolemic properties. Thus, Streptomyces is a rich source of the secondary metabolites in which common intermediates in the cell (amino acids, sugars, fatty acids, terpenes, etc.) are condensed into more complex st...

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“…pET15b and pET-HPPD were transformed into Escherichia coli cell line BL21(DE3) (Novagen) via electroporation. HPLC analysis of bacterial cultures for the presence of HGA was performed according to published procedures (Denoya et al, 1994). HGA was identified in extracts based on comparison of retention time and spectra to a HGA (Sigma) standard with a Hewlett-Packard series 1100 chromatograph and photodiode array detector.…”

Section: Protein Overexpressionmentioning

confidence: 99%

Complementation of the Arabidopsispds1Mutation with the Gene Encodingp-Hydroxyphenylpyruvate Dioxygenase

1998

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Plastoquinone and tocopherols are the two major quinone compounds in higher plant chloroplasts and are synthesized by a common pathway. In previous studies we characterized two loci in Arabidopsis defining key steps of this biosynthetic pathway. Mutation of the PDS1 locus disrupts the activity of p-hydroxyphenylpyruvate dioxygenase (HPPDase), the first committed step in the synthesis of both plastoquinone and tocopherols in plants. Although plants homozygous for the pds1 mutation could be rescued by growth in the presence of homogentisic acid, the product of HPPDase, we were unable to determine if the mutation directly or indirectly disrupted HPPDase activity. This paper reports the isolation of a cDNA, pHPPD, encoding Arabidopsis HPPDase and its functional characterization by expression in both plants and Escherichia coli. pHPPD encodes a 50-kD polypeptide with homology to previously identified HPPDases, including 37 highly conserved amino acid residues clustered in the carboxyl region of the protein. Expression of pHPPD in E. coli catalyzes the accumulation of homogentisic acid, indicating that it encodes a functional HPPDase enzyme. Mapping of pHPPD and co-segregation analysis of the pds1 mutation and the HPPD gene indicate tight linkage. Constitutive expression of pHPPD in a pds1 mutant background complements this mutation. Finally, comparison of the HPPD genomic sequences from wild type and pds1 identified a 17-bp deletion in the pds1 allele that results in deletion of the carboxyterminal 26 amino acids of the HPPDase protein. Together, these data conclusively demonstrate that pds1 is a mutation in the HPPDase structural gene.

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A Streptomyces avermitilis gene encoding a 4-hydroxyphenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli

Cited by 86 publications

References 47 publications

The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

The C‐terminal of rat 4‐hydroxyphenylpyruvate dioxygenase is indispensable for enzyme activity

Genome sequence of an industrial microorganism Streptomyces avermitilis : Deducing the ability of producing secondary metabolites

Complementation of the Arabidopsispds1Mutation with the Gene Encodingp-Hydroxyphenylpyruvate Dioxygenase

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