The shikimate pathway. Part 8. Synthesis of (−)-3(R)-amino-4(R),5(R)-dihydroxy-1-cyclohexene-1-carboxylic acid: The 3(R)-amino analogue of (−)-shikimic acid

Tetrahedron ◽  
1996 ◽  
Vol 52 (25) ◽  
pp. 8565-8580 ◽  
Author(s):  
Harry Adams ◽  
Neil A. Bailey ◽  
Roger Brettle ◽  
Richard Cross ◽  
Martyn Frederickson ◽  
...  
ChemInform ◽  
2010 ◽  
Vol 27 (40) ◽  
pp. no-no
Author(s):  
H. ADAMS ◽  
N. A. BAILEY ◽  
R. BRETTLE ◽  
R. CROSS ◽  
M. FREDERICKSON ◽  
...  

1999 ◽  
Vol 43 (1) ◽  
pp. 175-177 ◽  
Author(s):  
Glenn A. McConkey

ABSTRACT The shikimate pathway presents an attractive target for malaria chemotherapy. Three shikimic acid analogs exhibited different effects on Plasmodium falciparum growth. (6R)-6-Fluoro-shikimate and (6S)-6-fluoro-shikimate inhibited growth (50% inhibitory concentrations, 1.5 × 10−5 and 2.7 × 10−4 M, respectively), whereas 2-fluoro-shikimate had no effect. para-Aminobenzoic acid abrogated the inhibition, demonstrating that the shikimate pathway was specifically targeted.


ChemInform ◽  
2010 ◽  
Vol 27 (24) ◽  
pp. no-no
Author(s):  
R. BRETTLE ◽  
R. CROSS ◽  
M. FREDERICKSON ◽  
E. HASLAM ◽  
G. M. DAVIES

1998 ◽  
Vol 180 (9) ◽  
pp. 2541-2548 ◽  
Author(s):  
Dmitri V. Mavrodi ◽  
Vladimir N. Ksenzenko ◽  
Robert F. Bonsall ◽  
R. James Cook ◽  
Alexander M. Boronin ◽  
...  

ABSTRACT Pseudomonas fluorescens 2-79 produces the broad-spectrum antibiotic phenazine-1-carboxylic acid (PCA), which is active against a variety of fungal root pathogens. In this study, seven genes designated phzABCDEFG that are sufficient for synthesis of PCA were localized within a 6.8-kbBglII-XbaI fragment from the phenazine biosynthesis locus of strain 2-79. Polypeptides corresponding to allphz genes were identified by analysis of recombinant plasmids in a T7 promoter/polymerase expression system. Products of thephzC, phzD, and phzE genes have similarities to enzymes of shikimic acid and chorismic acid metabolism and, together with PhzF, are absolutely necessary for PCA production. PhzG is similar to pyridoxamine-5′-phosphate oxidases and probably is a source of cofactor for the PCA-synthesizing enzyme(s). Products of thephzA and phzB genes are highly homologous to each other and may be involved in stabilization of a putative PCA-synthesizing multienzyme complex. Two new genes, phzXand phzY, that are homologous to phzA andphzB, respectively, were cloned and sequenced from P. aureofaciens 30-84, which produces PCA, 2-hydroxyphenazine-1-carboxylic acid, and 2-hydroxyphenazine. Based on functional analysis of the phz genes from strains 2-79 and 30-84, we postulate that different species of fluorescent pseudomonads have similar genetic systems that confer the ability to synthesize PCA.


1981 ◽  
Vol 36 (3-4) ◽  
pp. 210-214 ◽  
Author(s):  
Jochen Berlin ◽  
Ludger Witte

To study the flow of carbon through the shikimate pathway in tobacco cell cultures with low and high yields of cinnamoyl putrescines, the cell cultures were treated with glyphosate. In the presence of glyphosate the levels of free shikimic acid were increased more than 300-fold by both cell lines. Despite of a normally 10-fold higher level of cinnamoyl putrescines, the high yielding cell line accumulated only 25% more free shikimic acid than the low yielding cell line. This result together with earlier observations indicated that the increased formation of cinnamoyl putrescines was rather limited by the activity of phenylalanine ammonia lyase than by increased substrate supply caused by alterations in the shikimate pathway


1968 ◽  
Vol 46 (8) ◽  
pp. 925-929 ◽  
Author(s):  
P. C. Chang ◽  
A. C. Blackwood

Pyocyanine, phenazine-1-carboxylic acid, and oxychlororaphine are produced simultaneously by Pseudomonas aeruginosa Mac 436 in certain media. When 14C-labelled substrates were supplied, the labelled carbon was incorporated into each of the pigments in varying amounts and also into CO2 and cells. Incorporation of labelled carbon from glycerol-1,3-14C and glycerol-2-14C was better than from shikimic-1,6-14C acid, and much better than from glucose-1-14C, -2-14C, or -6-14C, succinic-1,4-14C or -2,3-14C acid, or acetic-1-14C or -2-14C acid. The data suggest that all three pigments are synthesized through the same route although some variations in the results are difficult to explain. The conclusion is that the shikimic acid pathway is the probable route of synthesis.


2019 ◽  
Author(s):  
Robin Mesnage ◽  
Maxime Teixeira ◽  
Daniele Mandrioli ◽  
Laura Falcioni ◽  
Quinten Raymond Ducarmon ◽  
...  

AbstractThere is intense debate as to whether glyphosate can interfere with aromatic amino acid biosynthesis in microorganisms inhabiting the gastrointestinal tract, which could potentially lead to negative health outcomes. We have addressed this major gap in glyphosate toxicology by using a multi-omics strategy combining shotgun metagenomics and metabolomics. We tested whether glyphosate (0.5, 50, 175 mg/kg bw/day), or its representative EU commercial herbicide formulation MON 52276 at the same glyphosate equivalent doses, has an effect on the rat gut microbiome in a 90-day subchronic toxicity test. Clinical biochemistry measurements in blood and histopathological evaluations showed that MON 52276 but not glyphosate was associated with statistically significant increase in hepatic steatosis and necrosis. Similar lesions were also present in the liver of glyphosate-treated groups but not in the control group. Caecum metabolomics revealed that glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase in the shikimate pathway as evidenced by an accumulation of shikimic acid and 3-dehydroshikimic acid. Levels of caecal microbiome dipeptides involved in the regulation of redox balance (γ-glutamylglutamine, cysteinylglycine, valylglycine) had their levels significantly increased. Shotgun metagenomics showed that glyphosate affected caecum microbial community structure and increased levels of Eggerthella spp. and Homeothermacea spp.. MON 52276, but not glyphosate, increased the relative abundance of Shinella zoogleoides. Since Shinella spp. are known to degrade alkaloids, its increased abundance may explain the decrease in solanidine levels measured with MON 52776 but not glyphosate. Other glyphosate formulations may have different effects since Roundup® GT Plus inhibited bacterial growth in vitro at concentrations at which MON 52276 did not present any visible effect. Our study highlights the power of a multiomics approach to investigate effects of pesticides on the gut microbiome. This revealed the first biomarker of glyphosate effects on rat gut microbiome. Although more studies will be needed to ascertain if there are health implications arising from glyphosate inhibition of the shikimate pathway in the gut microbiome, our findings can be used in environmental epidemiological studies to understand if glyphosate can have biological effects in human populations.Graphical Abstract


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