From glucose to aromatics: recent developments in natural products of the shikimic acid pathway

Ganem, Bruce

doi:10.1016/0040-4020(78)80222-1

Cited by 169 publications

(56 citation statements)

References 218 publications

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“…If so, strong reducing agents might act to reverse the binding, thereby destabilizing the enzyme over time, as observed. A reaction mechanism for DAHP synthase that involves such an enzyme-phosphoenolpyruvyl intermediate coupled by a covalent thiol linkage has been proposed (11). DAHPS(Trp) as a metalloenzyme.…”

Section: Discussionmentioning

confidence: 99%

Purification and properties of tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli

Ray

Bauerle

1991

J Bacteriol

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The aroH gene of Escherichia coli, which encodes the tryptophan-sensitive 3-deoxy-n-arabino-heptulosonate-7-phosphate synthase isoenzyme of the common aromatic biosynthetic pathway, was cloned behind the tac promoter in expression plasmid pKK223-3. The enzyme was overexpressed, purified to homogeneity, and characterized. The native enzyme was found to be a dimeric metalloprotein containing 0.3 mol of iron per mol of subunit and variable amounts of zinc. The activity of the native enzyme was stimulated two-to threefold when assayed in the presence of Fe2+ ions. Pretreatment of the enzyme with Fe2+ also resulted in activation, accompanied by an equivalent increase in iron content. Treatment of the enzyme with chelating agents led to inactivation, which was fully reversed by the presence of Fe2+ in the assay mixture. The native enzyme exhibited a unique absorption profile, having a shoulder of absorbance on the aromatic band with a maximum around 350 nm and a broad, weak band with a maximum around 500 nm. Treatment of the enzyme with Fe2t enhanced the absorbance at 350 nm and eliminated the band at 500 nm. Treatment with reducing agents caused the disappearance of both bands and destabilized the enzyme. Feedback regulation of the activity of the enzyme was specific for tryptophan, with maximum inhibition at about 70%.In bacteria, a common aromatic pathway of seven steps leads to the synthesis of chorismic acid, the branch point precursor of the aromatic amino acids tryptophan, tyrosine, and phenylalanine, as well as of folic acid, ubiquinone, menaquinone, and enterochelin. The first committed step of this pathway is the condensation of erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP), yielding the phosphorylated 7-carbon keto sugar acid 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP). The enzyme that catalyzes this reaction is DAHP synthase (EC 4.1.2.15).In Escherichia coli there are three DAHP synthase isoenzymes, each specifically feedback regulated by one of the three aromatic amino acids (6). The Phe-sensitive [DAHP-S(Phe)] and Tyr-sensitive [DAHPS(Tyr)] isoenzymes, encoded by aroG and aroF, respectively, are responsible for essentially all of the DAHP synthase activity in the wild-type cell; the Trp-sensitive isoenzyme [DAHPS(Trp)], encoded by aroH, contributes only about 1% of the total activity (29). Molecular cloning and DNA sequencing of the aroF, aroG, and aroH genes (8,21,26) have revealed that the three polypeptides are nearly identical in size and have a high degree of sequence similarity. On this basis, it has been concluded that the three are homologs with a common evolutionary origin (19,21). DAHPS(Tyr) (1, 24) and DAHP-S(Phe) (17) from E. coli have been purified to homogeneity and extensively characterized; however, only a preliminary study of a partially purified preparation of DAHPS(Trp) has been reported (7). DAHPS(Phe) from E. coli is tetrameric in structure, while Bacterial strains and plasmids. E. coli AB3248 (aroF363 aroG365 aroH367 proA2 argE3 his4 thi lac gal-2 tsx-358) (31) and...

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Section: Discussionmentioning

confidence: 99%

Purification and properties of tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli

Ray

Bauerle

1991

J Bacteriol

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“…Proposed mechanisms include an X-group mechanism, involving the nucleophilic attack of the C-1 position of the substrate (5) (Scheme 2d), and a cationic mechanism, involving the step-wise loss of phosphate and a proton (11,12) (Scheme 2a). An allylic rearrangement of phosphate followed by a 1,2-elimination (13) has been discounted because the intermediate iso-EPSP is a competitive inhibitor rather than a substrate of the Neurospora crassa enzyme (14).…”

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confidence: 99%

Escherichia coli Chorismate Synthase Catalyzes the Conversion of (6S)-6-Fluoro-5-enolpyruvylshikimate-3-phosphate to 6-Fluorochorismate

Bornemann

Ramjee

Balasubramanian

et al. 1995

Journal of Biological Chemistry

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Chorismate synthase (EC 4.6.1.4) is the seventh enzyme of the shikimate pathway (1, 2) and catalyzes the conversion of 5-enolpyruvylshikimate-3-phosphate 1 (EPSP) 1 to chorismate 2 (Scheme 1). Chorismate is a common intermediate in the biosynthesis of aromatic metabolites such as aromatic amino acids and folate cofactors. The chorismate synthase reaction involves the 1,4-elimination of phosphate and the C-(6proR) hydrogen with overall anti-stereochemistry (3-5). A concerted elimination appears to be unlikely since studies with model systems (6, 7) and molecular orbital considerations (8, 9) suggest that concerted 1,4-eliminations with syn-stereochemistry are favored. For these reasons, several non-concerted mechanisms have been suggested for the chorismate synthase reaction (10). Proposed mechanisms include an X-group mechanism, involving the nucleophilic attack of the C-1 position of the substrate (5) (Scheme 2d), and a cationic mechanism, involving the step-wise loss of phosphate and a proton (11, 12) (Scheme 2a). An allylic rearrangement of phosphate followed by a 1,2-elimination (13) has been discounted because the intermediate iso-EPSP is a competitive inhibitor rather than a substrate of the Neurospora crassa enzyme (14).Reduced FMN is required for enzyme activity despite there being no overall reduction or oxidation in the conversion of EPSP to chorismate (15)(16)(17)(18)(19). The role of flavin is not yet clear but it appears to be directly involved in catalysis. A transient flavin intermediate has been characterized by uv/visible spectroscopy during single and multiple turnover experiments using the enzyme from Escherichia coli (20,21). It has been suggested that this spectrum is consistent with a charge transfer complex or a C-4a-flavin adduct (20). However, such a perturbation of the reduced flavin spectrum could, at least in part, be due to noncovalent interactions between the substrate and the flavin. The absence of detectable activity of the N. crassa (22) and E. coli (23) enzymes reconstituted with reduced 5-deaza-FMN provides additional evidence that reduced flavin is chemically, and not just structurally, involved in turnover. In the presence of the inhibitor (6R)-6-fluoro-EPSP the E. coli enzyme forms a protein-bound flavin semiquinone, suggesting the possibility of radical intermediates during normal turnover (24). A radical mechanism involving the initial abstraction of a hydrogen atom from the C-6 position of the substrate (11, 22, 25) seems unlikely since there are no obvious candidates for a catalytic center that can accept single electrons, such as transition metal ions (24), particularly given the requirement for fully reduced flavin for activity.

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“…19 Tannins and flavonoids also possess therapeutic uses due to their anti-inflammatory, antifungal, antioxidant, and healing properties. 20 Shikimic acid is an intermediate of the shikimic acid pathway 21 implicated in the synthesis of aromatic metabolites in plants and microorganisms. [22][23][24][25] Phenolic compounds, gallic acid and catechin, are widely found in plants.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study on Two Variants of Laghupanchamula (A Compound Ayurvedic Formulation) for Important Groups of Phytochemicals and Antioxidant Activity

Ghildiyal¹,

Joshi²,

Joshi³

2017

Journal of Drug Research in Ayurvedic Sciences

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Introduction: Laghupanchamula is a compound formulation prepared by combinations of roots of five herbs. Two variants of Laghupanchamula have been described in Ayurvedic classics where beside four common herbs fifth one is either Gokshura (Tribulus terrestris L.) or Eranda (Ricinus communis L.). The objective of the study is to make comparison between two variants of Laghupanchmula with respect to important group of phytochemicals and antioxidant activity to corroborate the science behind their therapeutic utility.

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From glucose to aromatics: recent developments in natural products of the shikimic acid pathway

Cited by 169 publications

References 218 publications

Purification and properties of tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli

Purification and properties of tryptophan-sensitive 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Escherichia coli

Escherichia coli Chorismate Synthase Catalyzes the Conversion of (6S)-6-Fluoro-5-enolpyruvylshikimate-3-phosphate to 6-Fluorochorismate

Comparative Study on Two Variants of Laghupanchamula (A Compound Ayurvedic Formulation) for Important Groups of Phytochemicals and Antioxidant Activity

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