Similarity between pyridoxal/pyridoxamine phosphate‐dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes

Pascarella, Stefano; Bossa, Francesco

doi:10.1002/pro.5560030418

Cited by 14 publications

(15 citation statements)

References 24 publications

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“…The EryCI family of proteins has been recognised as part of a large group of proteins involved in carbohydrate metabolism in either antibiotic or outer cell wall biosynthesis, and which appear to be aminotransferase or dehydrase enzymes dependent on pyridoxal phosphate or pyridoxamine phosphate as a cofactor (Thorson et al 1993;Piepersberg 1994;Pascarella and Bossa 1994). The sequence similarities are most marked in a region of the protein that contains the conserved lysine residue (Lys 258 in aspartate aminotransferase) which is the attachment site for pyridoxal phosphate (Piepersberg 1994;Pascarella and Bossa 1994) and the conserved aspartate residue (Asp-222 in aspartate aminotransferase) which makes a hydrogen bond with N1 of the pyridoxal ring (Pascarella and Bossa 1994) (Fig. 6).…”

Section: Resultsmentioning

confidence: 99%

Analysis of seven genes from the eryAI –eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea

Gaisser

Böhm²,

Cortés³

et al. 1997

Mol Gen Genet

111

149

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The gene cluster (ery) governing the biosynthesis of the macrolide antibiotic erythromycin A by Saccharopolyspora erythraea contains, in addition to the eryA genes encoding the polyketide synthase, two regions containing genes for later steps in the pathway. The region 5' of eryA, and lying between eryA and the gene eryK, which is known to encode the C-12 hydroxylase, has been sequenced and shown to contain seven additional open reading frames (ORFs 13-19). On the basis of sequence similarities, roles are proposed for several of these ORFs in the biosynthesis of the deoxysugar mycarose and the deoxyaminosugar desosamine. A chromosomal mutant carrying a deletion in ORF15 has been constructed and shown to accumulate 3-O-mycarosylerythronolide B, as expected for an eryC mutant. Similarly, a chromosomal mutant carrying a deletion in ORF16 has been constructed and shown to accumulate erythronolide B, as expected for an eryB mutant.

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Section: Resultsmentioning

confidence: 99%

Analysis of seven genes from the eryAI –eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea

Gaisser

Böhm²,

Cortés³

et al. 1997

Mol Gen Genet

111

149

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“…2). The α family also includes gene products that catalyze reactions in the biosynthesis of deoxyamino and dideoxy sugars with either PLP or pyridoxamine‐5′‐phosphate as a prosthetic group 16–20. These gene products are not listed in Figure 2 as their precise catalytic functions are unknown.…”

Section: Evolutionary Lineages Of B6 Enzymesmentioning

confidence: 99%

From cofactor to enzymes. The molecular evolution of pyridoxal‐5′‐phosphate‐dependent enzymes

Christen

Mehta

2001

The Chemical Record

178

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The pyridoxal-5'-phosphate (vitamin B(6))-dependent enzymes that act on amino acid substrates have multiple evolutionary origins. Thus, the common mechanistic features of B(6) enzymes are not accidental historical traits but reflect evolutionary or chemical necessities. The B(6) enzymes belong to four independent evolutionary lineages of paralogous proteins, of which the alpha family (with aspartate aminotransferase as the prototype enzyme) is by far the largest and most diverse. The considerably smaller beta family (tryptophan synthase beta as the prototype enzyme) is structurally and functionally more homogenous. Both the D-alanine aminotransferase family and the alanine racemase family consist of only a few enzymes. The primordial pyridoxal-5'-phosphate-dependent protein catalysts apparently first diverged into reaction-specific protoenzymes, which then diverged further by specializing for substrate specificity. Aminotransferases as well as amino acid decarboxylases are found in two different evolutionary lineages, providing examples of convergent enzyme evolution. The functional specialization of most B(6) enzymes seems to have already occurred in the universal ancestor cell before the divergence of eukaryotes, archebacteria, and eubacteria 1500 million years ago. Pyridoxal-5'-phosphate must have emerged very early in biological evolution; conceivably, metal ions and organic cofactors were the first biological catalysts. To simulate particular steps of molecular evolution, both the substrate and reaction specificity of existent B(6) enzymes were changed by substitution of active-site residues, and monoclonal pyridoxal-5'-phosphate-dependent catalytic antibodies were produced with selection criteria that might have been operative in the evolution of protein-assisted pyridoxal catalysis.

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“…Refs. [42][43][44][45]. Of the products of these genes, at the time of our work, only the AscC protein had been studied in detail.…”

Section: -Amino-5-hydroxybenzoic Acid Synthasementioning

confidence: 99%

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

Kim

Fryhle

et al. 1998

Journal of Biological Chemistry

112

116

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The biosynthesis of ansamycin antibiotics, like rifamycin B, involves formation of 3-amino-5-hydroxybenzoic acid (AHBA) by a novel variant of the shikimate pathway. AHBA then serves as the starter unit for the assembly of a polyketide which eventually links back to the amino group of AHBA to form the macrolactam ring. The terminal enzyme of AHBA formation, which catalyzes the aromatization of 5-deoxy-5-amino-3-dehydroshikimic acid, has been purified to homogeneity from Amycolatopsis mediterranei, the encoding gene has been cloned, sequenced, and overexpressed in Escherichia coli. The recombinant enzyme, a (His) 6 fusion protein, as well as the native one, are dimers containing one molecule of pyridoxal phosphate per subunit. Mechanistic studies showed that the enzyme-bound pyridoxal phosphate forms a Schiff's base with the amino group of 5-deoxy-5-amino-3-dehydroshikimic acid and catalyzes both an ␣,␤-dehydration and a stereospecific 1,4-enolization of the substrate. Inactivation of the gene encoding AHBA synthase in the A. mediterranei genome results in loss of rifamycin formation; production of the antibiotic is restored when the mutant is supplemented with AHBA.

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Similarity between pyridoxal/pyridoxamine phosphate‐dependent enzymes involved in dideoxy and deoxyaminosugar biosynthesis and other pyridoxal phosphate enzymes

Cited by 14 publications

References 24 publications

Analysis of seven genes from the eryAI –eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea

Analysis of seven genes from the eryAI –eryK region of the erythromycin biosynthetic gene cluster in Saccharopolyspora erythraea

From cofactor to enzymes. The molecular evolution of pyridoxal‐5′‐phosphate‐dependent enzymes

3-Amino-5-hydroxybenzoic Acid Synthase, the Terminal Enzyme in the Formation of the Precursor of mC7N Units in Rifamycin and Related Antibiotics

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