l-tryptophan

Thiostrepton (TSR), an archetypal member of the family of ribosomally synthesized and post-translationally modified thiopeptide antibiotics, possesses a biologically important quinaldic acid (QA) moiety within the side-ring system of its characteristic thiopeptide framework. QA is derived from an independent L-Trp residue; however, its associated transformation process remains poorly understood. We here report that during the formation of QA, the key expansion of an indole to a quinoline relies on the activities of the pyridoxal-5'-phosphate-dependent protein TsrA and the flavoprotein TsrE...

The development of electrochemical methods for enantioselective recognition is a focus of research in pharmaceuticals and biotechnology. In this study, a pair of water-soluble chiral 3,4-ethylenedioxythiophene (EDOT) derivatives-(R)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((R)-EDTM) and (S)-2'-hydroxymethyl-3,4-ethylenedioxythiophene ((S)-EDTM)-were synthesized and electrodeposited on the surface of a glassy carbon electrode (GCE) via current-time (I-t) polymerization in an aqueous LiClO4 electrolyte. These chiral PEDOT polymers were used to fabricate chiral sensors and to investigate the enantioselective recognition of D-/L-3,4-dihydroxyphenylalanine, D-/L-tryptophan and (R)-/(S)-propranolol enantiomers, respectively...

Conifers contain P450 enzymes from the CYP79 family that are involved in cyanogenic glycoside biosynthesis. Cyanogenic glycosides are secondary plant compounds that are widespread in the plant kingdom. Their biosynthesis starts with the conversion of aromatic or aliphatic amino acids into their respective aldoximes, catalysed by N-hydroxylating cytochrome P450 monooxygenases (CYP) of the CYP79 family. While CYP79s are well known in angiosperms, their occurrence in gymnosperms and other plant divisions containing cyanogenic glycoside-producing plants has not been reported so far...

The modified quantum dots (QDs), have been used in intracellular probing and drug delivery because of their special chemical and physical properties. In this paper, two β-cyclodextrin (β-CD)-modified CdSe/ZnS QDs with strong optical emission properties were synthesized as drug carriers to induce apoptosis. The positively charged L-Arginine (L-Arg) and neutral L-Tryptophan (L-Trp) were selected as ligands to compare the effect of charge on bioactivity of QDs nanoparticles. The in vitro assays revealed that these modified QDs showed good Dox carrier ability and significantly high inhibition rate to cancer cells...

Metal-organic frameworks (MOFs) are investigated for the adsorption of aromatic amino acids L-phenylalanine (L-Phe), L-tryptophan (L-Trp) and L-tyrosine (L-Tyr) from aqueous solutions. After screening a range of water-stable MOFs, the hydrophobic Zr-MOF MIL-140C emerged as the most performant material, exhibiting uptakes of 15 wt% for L-Trp and 20 wt% for L-Phe. These uptakes are 5 to 10 wt% higher than those of large-pore zeolites Beta and Y. Both single-compound and competitive adsorption isotherms for L-Phe and L-Trp were experimentally obtained at the natural pH of these amino acid mixtures without additional pH-modification (pH 6...

L-tryptophan is an essential amino acid widely used in food and pharmaceutical industries. However, its production via Escherichia coli fermentation suffers severely from both low glucose conversion efficiency and acetic acid inhibition, and to date effective process control methods have rarely been explored to facilitate its industrial scale production. To resolve these challenges, in the current research an engineered strain of Escherichia coli was used to overproduce L-tryptophan. To achieve this, a novel dynamic control strategy which incorporates an optimised anthranilic acid feeding into a dissolved oxygen-stat (DO-stat) glucose feeding framework was proposed for the first time...

The objective of this study was to provide in ovo evidence for the proposed role of kynurenine formamidase of l-tryptophan to NAD(+) pathway in embryo yolk sac membranes as a primary target for organophosphorus insecticide (OPI) teratogens in OPI-induced NAD-associated avian teratogenesis. Slices prepared from yolk sac membranes or embryo livers of chicken eggs treated with the OPI dicrotophos and/or methyl parathion were incubated with l-tryptophan. Yolk sac membrane slices metabolized l-tryptophan in the pathway to NAD(+) before that function was established in livers...

Four novel amino acid-functionalised triphenylenes have been prepared with glycine, l-alanine, l-phenylalanine and l-tryptophan ethyl ester side-chains. The glycine derivative is a good gelator of chloroform, the alanine derivative gels ethanol and toluene, and the phenylalanine derivative gels benzene and toluene. The tryptophan derivative does not gel any of the solvents tested, most probably due to its more bulky structure, but forms microspheres by evaporation-induced self-assembly. The self-assembly properties of the π-gelators have been investigated using infrared, UV-absorption and fluorescence spectroscopy, concentration- and temperature-dependent NMR, and X-ray scattering experiments on dried xerogel as well as the wet organogel...

Psilocybin is the psychotropic tryptamine-derived natural product of Psilocybe carpophores, the so-called "magic mushrooms". Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes. These include i) PsiD which represents a new class of fungal l-tryptophan decarboxylases, ii) PsiK, that catalyzes the phosphotransfer step, iii) the methyl transferase PsiM, catalyzing iterative N-methyltransfer as terminal biosynthetic step, and iv) PsiH, a monooxygenase...

TsrM catalyzes the methylation of C2 in Ltryptophan (Trp). This reaction is the first step in the biosynthesis of the quinaldic acid moiety of the thiopeptide antibiotic thiostrepton, which exhibits potent activity against Gram-positive pathogens. TsrM is a member of the radical S-adenosylmethionine (SAM) superfamily of enzymes, but does not catalyze formation of 5'-deoxyadenosin-5'-yl or any other SAM-derived radical. In addition to a [4Fe-4S] cluster, TsrM contains a cobalamin cofactor that serves as an intermediate methyl carrier in its reaction...

Indoleamine 2,3-dioxygenase-1 (IDO-1) catalyses the first and rate-limiting step in the metabolism of L-tryptophan. Degradation of L-Trp leads to the production of several immunosuppressive metabolites, including N-formyl kynurenine and kynurenine (Kyn). Apart from a normal physiological role, IDO-1 has also been identified to play a crucial role in immune suppression and tumour induced tolerance. Indeed, many primary tumours express high levels of IDO-1 compared to normal cells of the same stroma. IDO-1 is accepted as being an inducible negative regulator of T cell viability, proliferation and activation...

The ability of positively charged aggregates of the surfactant (1R,2S)-Dodecyl(2-hydroxy-1-methyl-2-phenylethyl)dimethylammonium bromide (DMEB) to incorporate D- or L-tryptophan in the gas-phase has been investigated by electrospray ion mobility mass spectrometry (ESI-IM-MS). Strongly impacted by the pH of the electrosprayed solutions, both protonated (T(+) ) and deprotonated (T(-) ) tryptophan are effectively included into the aggregates whereas, tryptophan in zwitterionic (T(0) ) form is practically absent in singly charged DMEB aggregates but can be found in multiply charged ones...

d- and l-Tryptophan (Trp) and d- and l-kynurenine (KYN) were derivatized with a chiral reagent, (S)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS), and were separated enantiomerically by high-performance liquid chromatography (HPLC) equipped with a triazole-bonded column (Cosmosil HILIC) using tandem mass spectrometric (MS/MS) detection. Effects of column temperature, salt (HCO2 NH4 ) concentration, and pH of the mobile phase in the enantiomeric separation, followed by MS detection of (S)-DBD-PyNCS-d,l-Trp and -d,l-KYN, were investigated...

Escherichia coli FB-04(pta1), a recombinant L-tryptophan production strain, was constructed in our laboratory. However, the conversion rate (L-tryptophan yield per glucose) of this strain is somewhat low. In this study, additional genes have been deleted in an effort to increase the conversion rate of E. coli FB-04(pta1). Initially, the pykF gene, which encodes pyruvate kinase I (PYKI), was inactivated to increase the accumulation of phosphoenolpyruvate, a key L-tryptophan precursor. The resulting strain, E...

The human heme enzyme tryptophan 2,3-dioxygenase (hTDO) catalyzes the insertion of dioxygen into its cognate substrate, l-tryptophan (l-Trp). Its active site structure is highly dynamic, and the mechanism of enzyme-substrate-ligand complex formation and the ensuing enzymatic reaction is not yet understood. Here we have studied complex formation in hTDO by using time-resolved optical and infrared spectroscopy with carbon monoxide (CO) as a ligand. We have observed that both substrate-free and substrate-bound hTDO coexist in two discrete conformations with greatly different ligand binding rates...

Trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) is a cyclic β-amino acid that can be used for the synthesis of chiral materials and nonnatural peptides. The aim of this study was to accumulate DHHA by engineering Pseudomonas chlororaphis GP72, a nonpathogenic strain that produces phenazine-1-carboxylic acid and 2-hydroxyphenazine. First, the phzF deletion mutant DA1 was constructed, which produced 1.91 g/L DHHA. Moreover, rpeA and pykF were disrupted and then ppsA and tktA were co-expressed in strain DA1...

Natural amino acids are well known to form coordination polymers with transition metal ions. In this study, six homochiral metal-organic frameworks constructed from Zn(2+) or Co(2+) ions and various enantiopure amino acid (L-tyrosine, L-histidine, L-tryptophan and L-glutamic acid), namely [Zn(L-tyr)]n (L-tyrZn), [Zn4 (btc)2 (Hbtc)(L-His)2 (H2 O)4 ]·1.5H2 O, {[Zn2 (L-trp)2 (bpe)2 (H2 O)2 ]·2H2 O·2NO3 }n , [Co2 (L-Trp)(INT)2 (H2 O)2 (ClO4 )], [Co2 (sdba)((L-Trp)2 ] and [Co(L-Glu)(H2 O)·H2 O]∞ , were synthesized according to the methods previously reported in the literature...

Deep sea sediment samples of Bay of Bengal (Visakhapatnam) have been analyzed for actinomycetes as an elite source to screen for the production of bioactive metabolites. The actinomycetes strain VSM-30 has an exciting bioactivity profile and was isolated during our systemic screening of marine actinomycetes. It was identified as Streptomyces sparsus based on morphological, physiological, biochemical, and molecular approaches. Response surface methodology regression analysis was carried out to fit the experimental data of each response by the second-order polynomial...

The primary headache disorders include migraine, which is one of the most frequent neurological disorders, which influences more than 14% of the whole population. Despite the research efforts, its exact pathomechanism is not fully revealed, but evidence points to the role of glutamate and its receptors. Kynurenic acid is an endogenous glutamate receptor antagonist produced by the kynurenine pathway (KP). Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) convert l-tryptophan to N-formyl-l-kynurenine, to be further transformed to l-kynurenine...

Liver fibrosis, a precursor to cirrhosis, is the result of the deposition of extracellular matrix (ECM) proteins and is mediated primarily by activated hepatic stellate cells (HSCs). In this study, we investigated the anti-fibrotic effects of interferon (IFN)-γ in activated HSCs in vitro and whether cell viability would be decreased by the inhibition of indoleamine 2,3-dioxygemase (IDO), which is responsible for cell cycle arrest. Following treatment with IFN-γ, cell signaling pathways and DNA content were analyzed to assess the inactivation of HSCs or the decrease in HSC proliferation...