Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: EC:6.2.1.1 (
ACS
)
78,556
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
A novel biosynthetic pathway was designed and verified reversely leading to the production of 5-hydroxytryptophan (5-HTP) from glucose. This pathway takes advantage of the relaxed substrate selectivities of relevant enzymes without employing the unstable
tryptophan 5-hydroxylase
. First, high-titer of 5-HTP was produced from 5-hydroxyanthranilate (5-HI) by the catalysis of E. coli TrpDCBA. Then, a novel salicylate 5-hydroxylase was used to convert the non-natural substrate anthranilate to 5-HI. After that, the production of 5-HI from glucose was achieved and optimized with modular optimization. In the end, we combined the full pathway and adopted a two-stage strategy to realize the de novo production of 5-HTP. This work demonstrated the application of enzyme promiscuity in non-natural pathway design.
ACS
Synth Biol 2015 May 15
PMID:Precursor-directed biosynthesis of 5-hydroxytryptophan using metabolically engineered E. coli. 2527 44
Methylenedioxymethamphetamine (MDMA; ecstasy) is used recreationally and has been investigated as an adjunct to psychotherapy. Most acute effects of MDMA can be attributed to activation of the serotonin (5-hydroxytryptamine [5-HT]) system. Genetic variants, such as single-nucleotide polymorphisms (SNPs) and polymorphic regions in 5-HT system genes, may contribute to interindividual differences in the acute effects of MDMA. We characterized the effects of common genetic variants within selected genes that encode the 5-HT system (
TPH1
[
tryptophan 5-hydroxylase
1] rs1800532 and rs1799913,
TPH2
[
tryptophan 5-hydroxylase
2] rs7305115,
HTR1A
[5-HT
1A
receptor] rs6295,
HTR1B
[5-HT
1B
receptor] rs6296,
HTR2A
[5-HT
2A
receptor] rs6313, and
SLC6A4
[serotonin transporter] 5-HTTLPR and rs25531) on the physiological and subjective response to 125 mg of MDMA compared with placebo in 124 healthy subjects. Data were pooled from eight randomized, double-blind, placebo-controlled studies that were conducted in the same laboratory.
TPH2
rs7305115,
HTR2A
rs6313, and
SLC6A4
5-HTTLPR polymorphisms tended to moderately alter some effects of MDMA. However, after correcting for multiple comparisons, none of the tested genetic polymorphisms significantly influenced the response to MDMA. Variations in genes that encode key targets in the 5-HT system did not significantly influence the effects of MDMA in healthy subjects. Interindividual differences in the 5-HT system may thus play a marginal role when MDMA is used recreationally or therapeutically.
ACS
Chem Neurosci 2019 07 17
PMID:Role of Serotonin Transporter and Receptor Gene Variations in the Acute Effects of MDMA in Healthy Subjects. 3058 33
