The biosynthesis of shikimate metabolites

Knaggs, Andrew R.

doi:10.1039/a707501d

Cited by 35 publications

(27 citation statements)

References 57 publications

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“…DAHP is converted to the branch point compound chorismate (2)(3)(4)(5), which is a precursor for the aromatic amino acids tyrosine (Tyr), phenylalanine (Phe), and tryptophan (Trp). The latter two amino acids are synthesized only by microorganisms and plants (6) and are assimilated by animals with the diet.…”

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confidence: 99%

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Helmstaedt

Strittmatter

Lipscomb

et al. 2005

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

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The shikimate pathway resulting in three aromatic amino acids is initiated in different organisms by two and three 3-deoxy-D-arabino-heptulosonate-7-phosphate synthases, respectively. Aro3p and Aro4p are the yeast enzymes feedback-inhibited by phenylalanine and tyrosine, respectively. A yeast strain deficient in the general control transcriptional regulatory system of amino acid biosynthesis is unable to live in the presence of high amounts of phenylalanine and tyrosine. Here, we show that this yeast strain can be rescued by the expression of aroH from Escherichia coli encoding the tryptophan-regulated AroH as third isoenzyme. Yeast carrying Ec AroH as the only enzyme for the initial step of the shikimate pathway can grow in the absence of tryptophan. Without aromatic amino acids, this yeast strain survives only when the yeast ARO3 promoter instead of the ARO4 promoter drives E. coli aroH. The detailed analysis of Aro3p and Aro4p revealed a triple feedback control by tyrosine͞phenylalanine and tryptophan. Dissecting this control allowed engineering of Aro4p S195A as an enzyme, which is inhibited like AroH only by tryptophan. In addition, Aro4p variants were constructed that show an equally strong inhibition by tyrosine and tryptophan (Aro4p P165G Q302R) and in which the regulation by tyrosine and tryptophan was reversed (Aro4p P165G). Our data suggest that yeast possesses only two instead of three isogenes encoding 3-deoxy-D-arabinoheptulosonate-7-phosphate synthases because both isoenzymes can be fine tuned by tryptophan as additional effector and because transcriptional regulation by the general control system can be induced as backup when aromatic amino acids in the environment are imbalanced.general control ͉ Aro4p ͉ AroH

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confidence: 99%

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Helmstaedt

Strittmatter

Lipscomb

et al. 2005

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

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“…Several classes of natural products utilize aromatic amino acids or other metabolites derived from the shikimate pathway as precursors including flavonoids, alkaloids, and nonribosomal peptides (63). Increasing flux through the shikimate pathway or downstream amino acid tailoring steps has been used successfully to increase natural product yields.…”

Section: Metabolic Engineering For Strain Improvementmentioning

confidence: 99%

Metabolic Engineering for the Production of Natural Products

Pickens

Tang²,

Chooi³

2011

Annu. Rev. Chem. Biomol. Eng.

285

161

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Natural products and natural product derived compounds play an important role in modern healthcare as frontline treatments for many diseases and as inspiration for chemically synthesized therapeutics. With advances in sequencing and recombinant DNA technology, many of the biosynthetic pathways responsible for the production of these chemically complex and pharmaceutically valuable compounds have been elucidated. With an ever expanding toolkit of biosynthetic components, metabolic engineering is an increasingly powerful method to improve natural product titers and generate novel compounds. Heterologous production platforms have enabled access to pathways from difficult to culture strains; systems biology and metabolic modeling tools have resulted in increasing predictive and analytic capabilities; advances in expression systems and regulation have enabled the fine-tuning of pathways for increased efficiency, and characterization of individual pathway components has facilitated the construction of hybrid pathways for the production of new compounds. These advances in the many aspects of metabolic engineering have not only yielded fascinating scientific discoveries but also make it an increasingly viable approach for the optimization of natural product biosynthesis.

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“…The two most well-known members of this family of enzymes are the mechanistically distinct MIP synthases and dehydroquinate (DHQ) synthases. The MIP synthases catalyze the conversion of D-glucose 6-phosphate to 1L- myo -inositol 1-phosphate, the first committed step in the production of all inositol-containing compounds including some aminoglycoside antibiotics, and the DHQ synthases catalyze the conversion of the C 7 -sugar phosphate, 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP), to 3-dehydroquinic acid in the shikimate pathway [11,12]. …”

Section: The Diversity Of Sugar Phosphate Cyclasesmentioning

confidence: 99%

Progress in aminocyclitol biosynthesis

Mahmud

2009

Current Opinion in Chemical Biology

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Summary A stream of genetic and biochemical information available for the biosynthesis of aminocyclitols over the past few years has provided the foundation to study the modes of formation of this clinically important class of natural products. In addition to work on the identification and functional analysis of aminocyclitol biosynthetic gene clusters, a contingent of recent studies has focused on the detailed analysis of unique enzymatic and catalytic mechanisms inherent to these pathways. The results provide invaluable insights into the biochemical and molecular aspects of aminocyclitol biosynthesis and have revealed diverse and unique features of the pathways.

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The biosynthesis of shikimate metabolites

Cited by 35 publications

References 57 publications

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Evolution of 3-deoxy- d - arabino -heptulosonate-7-phosphate synthase-encoding genes in the yeast Saccharomyces cerevisiae

Metabolic Engineering for the Production of Natural Products

Progress in aminocyclitol biosynthesis

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