HOMOSERINE LACTONE

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Positive Autoregulation of an Acyl Homoserine Lactone Quorum Sensing Circuit Synchronizes the Population Response

Positive Autoregulation of an Acyl Homoserine Lactone Quorum Sensing Circuit Synchronizes the Population Response

ABSTRACT Many proteobacteria utilize acyl-homoserine lactone quorum-sensing signals. At low population densities, cells produce a basal level of signal, and when sufficient signal has accumulated in the surrounding environment, it binds to its re- ceptor, and quorum-sensing-dependent genes can be activated. A common charac- teristic of acyl-homoserine lactone quorum sensing is that signal production is posi- tively autoregulated. We have examined the role of positive signal autoregulation in Pseudomonas aeruginosa. We compared population responses and individual cell re- sponses in populations of wild-type P. aeruginosa to responses in a strain with the signal synthase gene controlled by an arabinose-inducible promoter so that signal was produced at a constant rate per cell regardless of cell population density. At a population level, responses of the wild type and the engineered strain were in- distinguishable, but the responses of individual cells in a population of the wild type showed greater synchrony than the responses of the engineered strain. Al- though sufficient signal is required to activate expression of quorum-sensing- regulated genes, it is not sufficient for activation of certain genes, the late genes, and their expression is delayed until other conditions are met. We found that late gene responses were reduced in the engineered strain. We conclude that positive signal autoregulation is not a required element in acyl-homoserine lactone quorum sensing, but it functions to enhance synchrony of the responses of individuals in a population. Synchrony might be advantageous in some situa- tions, whereas a less coordinated quorum-sensing response might allow bet hedging and be advantageous in other situations.

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Production of phenylacetyl-homoserine lactone analogs by artificial biosynthetic pathway in Escherichia coli

Production of phenylacetyl-homoserine lactone analogs by artificial biosynthetic pathway in Escherichia coli

known as p-coumaryl-homoserine lactone synthase, EC 2.3.1.229) with a p-coumaric acid rather than fatty acids [7, 8]. Schaefer et al. speculated that there is an intimate relationship between p-coumaroyl-HSL producing bac- teria and specific plants through p-coumaroyl-HSL sign- aling [7], because the rpaI gene expression is activated specifically by growth of R. palustris on p-coumaric acid [9], a major aromatic monomer of lignin, which comprise over 30 % of all plant dry material. It is clear that several photosynthetic bacteria and nitrogen-fixing bacteria respond in complex ways to the presence of exogenous lignin monomers and this may drive intercellular signal- ing for a metabolites’ production [7, 10]. These metabo- lites may comprise antibiotics and auxins that suppress the growth of potentially parasitic bacteria and promote algal growth, respectively [11–13]. It is a distinctly pos- sible scenario that phenylacetyl-HSL could serve an ecological role in these diverse QS pathways in natural environments.

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Han, Shengcai
  

(2017):


	Systemic responses of barley to the growth promoting, endophytic bacterium Acidovorax radicis N35 and role of 3-hydroxy-C10-homoserine lactone production in root colonization and plant perception.


Dissertation, LMU München:

Han, Shengcai (2017): Systemic responses of barley to the growth promoting, endophytic bacterium Acidovorax radicis N35 and role of 3-hydroxy-C10-homoserine lactone production in root colonization and plant perception. Dissertation, LMU München: Fakultät für Biologie

Acidovorax radicis N35 is a plant growth promoting endophytic bacterium in wheat and barley. The perception by plants can be characterized using RNAseq, q-PCR and selected metabolite analyses. It could be shown, that barley seedlings are quickly responding to bacterial colonization by a reprogramming of gene expression and priming of defense responses. Especially, the role of quorum sensing auto-inducers of the N-acyl homoserine lactone (AHL) type in the perception by plants should be analyzed. A. radicis N35 produces 3-hydroxy-C10-homoserine lactone (3-OH- C10-HSL) as major AHL-compound. In this communication the influence of A. radicis N35- produced 3-OH-C10-HSL on barley seedlings was investigated by comparing wild type and an araI insertion mutant, lacking AHL-production. The comparison of inoculation effects of the A. radicis N35 wild type and the araI::tet mutant discovered remarkable differences. While the N35 wild type colonized plant roots effectively by forming biofilm-like structures on the root surface, the araI::tet mutant occurred at the root surface as single cells. In addition, in a mixed inoculum of wild type and araI::tet mutant, the wild type was predominant in colonization compared to the araI::tet mutant. Nevertheless, a significant plant growth promotion effect could be shown after inoculation of barley with the wild type and the araI::tet mutant in soil after 2 months. A. radicis N35 wild type showed less induction of early defense responses in plant RNA-expression

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The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans

The Quorum-Sensing Molecules Farnesol/Homoserine Lactone and Dodecanol Operate via Distinct Modes of Action in Candida albicans

homoserine lactone, a quorum-sensing molecule secreted by Pseudomonas aeruginosa, block hyphal develop- ment by affecting cAMP signaling; they both directly inhibited the activity of the Candida adenylyl cyclase, Cyr1p. In contrast, the 12-carbon alcohol dodecanol appeared to modulate hyphal development and the cAMP signaling pathway without directly affecting the activity of Cyr1p. Instead, we show that dodecanol exerted its effects through a mechanism involving the C. albicans hyphal repressor, Sfl1p. Deletion of SFL1 did not affect the response to farnesol but did interfere with the response to dodecanol. Therefore, quorum sensing in C. albicans is mediated via multiple mechanisms of action. Interestingly, our experiments raise the possibility that the Burkholderia cenocepacia diffusible signal factor, BDSF, also mediates its effects via Sfl1p, suggesting that dodecanol’s mode of action, but not farnesol or 3-oxo-C 12 -homoserine lactone, may be used by other quorum-

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Acyl-Homoserine Lactone Based Modulators for RhlI, a Quorum Sensing Signal Synthase in Pseudomonas aeruginosa

Acyl-Homoserine Lactone Based Modulators for RhlI, a Quorum Sensing Signal Synthase in Pseudomonas aeruginosa

Gram-negative bacteria use N-acyl-homoserine lactone (AHL) autoinducer based signal system, known as quorum sensing (QS), to modulate the gene expression for such traits as biofilm formation, toxin production, and antibiotic resistance. Therefore, there is great potential in pursuing quorum sensing inhibition (QSI) as a means of achieving antivirulence. Pseudomonas aeruginosa, an opportunistic pathogen commonly found in healthcare-related infections, use two LuxI/R type systems to regulate AHL-based quorum sensing: LasI/R and RhlI/R. LasI (initiator protein/signal synthase) and LasR (receptor) use 3-oxododecanoyl-L-homoserine lactone signal molecule while RhlI and RhlR use butanoyl-L-homoserine lactone autoinducer. Thus far, most of the studies have focused on inhibiting the Las system, in particular by using AHL signal analogs to interfere with signal-receptor binding. Recently, RhlI/R system has gained attention as potentially having greater effect in P. aeruginosa virulence. In this study, we have tested the effect of AHL analogs on RhlI, as product inhibitors with the goal of targeting both RhlI and RhlR for increased potency. Screening of compounds have revealed three variations to have the greatest effect on RhlI inhibition: longer/bulkier acyl- chain, D- stereocenter in the headgroup, and a less polar thiolactone head-group. Surprisingly, the addition of a carbonyl at the C3 position was found to activate the enzyme. Moreover, we measured kinetic constants of RhlI with various acyl-substrates and performed inhibition assays with inert acyl-substrate analogs to determine how RhlI activity changes to

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Biochemical Detection of N-Acyl Homoserine Lactone from Biofilm-Forming Uropathogenic Escherichia coli Isolated from Urinary Tract Infection Samples

Biochemical Detection of N-Acyl Homoserine Lactone from Biofilm-Forming Uropathogenic Escherichia coli Isolated from Urinary Tract Infection Samples

homoserine lactone. R is a functional group that can be substituted by various fatty acid chains; for example, Pseudomonas aeruginosa (P. aeruginosa) relies on QS via production of the lactones N- butanoyl-l-homoserine (C4-HSL) and N-(3- oxododecanoyl)-l-HSL (3-oxo-C12-HSL) to regulate swarming, toxin and protease production, and proper biofilm formation. The absence of one or more components of the QS system can significantly reduce the pathogen’s virulence. Little information is available regarding the relation of AHL and biofilm formation in UPEC strains (7).

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SYNTHESIS OF N-BUTANOYL L-HOMOSERINE LACTONE A PHARMACEUTICALLY IMPORTANT QUORUM SENSING DRUG Mahendra N. Lokhande*, Nilesh V Rathod, Sachin A Khiste, Dnyneshwar S. WankhedeDOWNLOAD/VIEW

SYNTHESIS OF N-BUTANOYL L-HOMOSERINE LACTONE A PHARMACEUTICALLY IMPORTANT QUORUM SENSING DRUG Mahendra N. Lokhande*, Nilesh V Rathod, Sachin A Khiste, Dnyneshwar S. WankhedeDOWNLOAD/VIEW

The different varieties of N-acyl homoserine lactones (N-AHLs) produced by different bacteria and are differ in their length of the acylated side chain of amino lactone. These are small molecules as a part of quorum sensing system of bacteria and are used by bacteria during their virulence pathogenic involvement. Herein, we would like introduce a new synthetic approach for the synthesis of (R)-isomer of N-acylated homoserine lactone via L-proline catalyzed asymmetric α-amination reaction. Enantioselective synthesis of N-butanoyl-(R)-homoserine (1) lactone from 4-benzyloxy butyraldehyde (4) via L-proline catalyzed asymmetric α-amination of aldehyde. Synthesis of this target molecule is straightforward and completed in five steps with overall yield of 32% and 92% ee.

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Characterization of Acyl Homoserine Lactone of pigment producing Pseudomonas aeruginosa SU 3

Characterization of Acyl Homoserine Lactone of pigment producing Pseudomonas aeruginosa SU 3

AHLs isolated in this study showed retention times of 3.054 and 4.659 which is assigned for C4-HSL and C5-HSL respectively (Figure 2), whereas Lade et al [24] assigned retention time of 3.224 for C4-HSL and 6.296 for C6- HSL. Pseudomonas aeruginosa synthesizes N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL), which acts as a signaling molecule , regulates virulence factors and biofilm formation [25].

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Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66

Identification, synthesis and regulatory function of the N-acylated homoserine lactone signals produced by Pseudomonas chlororaphis HT66

might be 3-oxo or 3-OH-acyl-HSLs with side chains ranging from 6 to 10 carbons. To identify the signals more precisely, extracts were separated by preparative TLC, and then the corresponding parts were scrapped and dissolved in the sample for HPLC–MS/MS analy- sis. It is known that every member of the AHL family gives a particular lactone ring at a nominal mass of m/z 102.05 [35], which results from the cleavage of homoser- ine lactone ring at the N-acyclic side chain. This charac- teristic ion was the key to analyze AHLs by HPLC–MS/ MS. After MS/MS analysis, we found that three ions generated a peak for the characteristic ion at m/z 102.05 and some other peaks of fragmentations (Fig. 2a–c). For example, the 3-OH-C8-HSL has a molecular weight of 243, and the detected mass fragmentation [M + H] + was

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Crystal structure of N (3 oxo­butano­yl) L homoserine lactone

Crystal structure of N (3 oxo­butano­yl) L homoserine lactone

N-Acyl homoserine lactones (AHLs) mediate quorum sensing in Gram-negative bacteria (Miller & Bassler, 2001; Waters & Bassler, 2005). We have previously shown that AHLs engage in n!* interactions between the acyl and lactone ester carbonyl groups (Newberry & Raines, 2014). These inter- actions cause attraction through donation of oxygen lone pair (n) electron density into the * antibonding orbital of an acceptor carbonyl group (Hinderaker & Raines, 2003). This interaction is observed in the free molecule but not in struc- tures of these compounds bound to their protein receptors, implicating these interactions in the potency of AHLs and their analogs. Background to carbonyl–carbonyl interactions is given by Bretscher et al. (2001), DeRider et al. (2002), Hinderaker & Raines (2003), and Bartlett et al. (2010). Our previous studies were restricted to AHLs with simple acyl appendages, but natural AHLs are also often oxidized at the 3-position to yield -keto acyl groups, such as that reported here.

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Homoserine Toxicity in Saccharomyces cerevisiae and Candida albicans Homoserine Kinase (thr1Δ) Mutants

Homoserine Toxicity in Saccharomyces cerevisiae and Candida albicans Homoserine Kinase (thr1Δ) Mutants

What then is the toxic role of homoserine in the cell, and why does it result in such a plethora of phenotypes? We present evidence that homoserine acts as a toxic threonine analog; however, for three of the gene products that metabo- lize threonine, Cha1p, Ilv1p, or Gly1p, we did not observe any evidence of homoserine inhibition or metabolism. It remains possible that homoserine may act as an allosteric inhibitor of an unknown and/or important yeast gene product. Alterna- tively, homoserine may be converted to homoserine lactone, similar to the toxicity in mammalian cells caused by conversion of the structurally similar homocysteine to homocysteine thio- lactone (40); however, we see no evidence of homoserine lac- tone toxicity in THR1 or thr1 ⌬ strains (data not shown). A final process in which threonine is a substrate is translation. Homo- serine is likely not inhibiting threonine incorporation into pro- teins via inhibition of the threonyl-tRNA synthetase Ths1p, since overexpression of THS1 did not alleviate homoserine toxicity. Similarly, the lack of suppression of homoserine tox- icity by expression of the E. coli threonyl-tRNA synthetase, which does not aminoacylate homoserine (30), argues against a role for homoserine incorporation into proteins via only Ths1p-mediated aminoacylation. However, since translation is required for homoserine toxicity, homoserine may be mis- acylated by multiple aminoacyl tRNA synthetases, as is the case for homocysteine (12, 13, 41–44). Various homoserine- mediated deleterious phenotypes observed for thr1 ⌬ and thr4 ⌬ mutants would be consistent with homoserine incorporation into proteins, creating aberrant proteins that are sensitive to various stresses, analogous to effects mediated by the incorpo- ration into protein of toxic amino acid analogs (93, 96). If homoserine is incorporated into proteins causing misfolding, this would also be consistent with thr1 ⌬ and thr4 ⌬ being syn- thetic lethal with hsp82 ⌬ , an isoform of the chaperone HSP90 important for protein folding (68), and/or having increased sensitivity to HSP90 inhibitors (57, 97).

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Characterization of quorum sensing and quorum quenching soil bacteria isolated from malaysian tropical montane forest

Characterization of quorum sensing and quorum quenching soil bacteria isolated from malaysian tropical montane forest

Although different target genes are regulated by AHLs, the basic mechanisms of AHL biosynthesis and gene regulation seem to be conserved in different QS bacterial species [7]. Many of these bacteria possess a QS mechanism with the LuxI/LuxR signal-response circuit as the backbone with additional complexity. For instance, the phytopathogen Agrobacterium tumefaciens, which is responsible for crown gall tumors in plants, uses the tumour-derived opines and the transcriptional factor OccR or AccR to regulate the expression of the LuxR homologue TraR [8,9]. The opportunistic pathogen Pseudomonas aeruginosa employs two pairs of LuxI/LuxR like systems, namely LasI/R and RhlI/R, that function in tandem to regulate the expression of virulence factors and biofilm formation [10]. Another group of homoserine lactone known as p-coumaroylhomoserine lactone (pC-HSL) has been discovered to be produced by the photosynthetic bacterium Rhodopseudomonas palustris. Synthesis of pC-HSL molecules were catalyzed by RpaI, a LuxI homolog, which uses environmental p-coumaric acid rather than intracellular fatty acids as a pC-HSL precursor [11].

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Occurrence of N Acyl Homoserine Lactones in Extracts of Bacterial Strain of Pseudomonas aeruginosa and in Sputum Sample Evaluated by Gas Chromatography–Mass Spectrometry

Occurrence of N Acyl Homoserine Lactones in Extracts of Bacterial Strain of Pseudomonas aeruginosa and in Sputum Sample Evaluated by Gas Chromatography–Mass Spectrometry

Nowadays, the determination of AHLs is of great in- terest, and development of reliable and sensitive analyti- cal methods for their structural characterization can pro- vide the information to elucidate their biological signi- ficance and activities. A wide variety of analytical pro- cedures for the analysis of N-acyl homoserine lactones was developed and summarized in the literature [8-14, 20-25]. Screening for AHLs production from bacterial strains is based on bacteriological monitoring system, alone [8-10] or in simultaneous combination of these monitoring systems [11]. Using high performance liquid chromatography with tandem mass spectrometry in con- junction with chemical synthesis, Throup et al. [12] iden- tified two signal molecules and showed them to be N-hexanoyl-L- homoserine lactone (HHL) and N-3-oxo-hexanoyl-L- homoserine lactone (OHHL). The production of OHHL was confirmed by Jacobi et al. [13] by thin layer chromatography in combination with an Escherichia coli AHL biosensor. A robust method based on solid-phase extraction (SPE) followed by ultra high- pressure liquid chromatography is proposed for the de- termination of five derivatives of N-acyl homoserine lactones [14]. Pseudomonas aeruginosa is a highly rele- vant opportunistic pathogen and is the most common gram-negative bacterium found in nosocomial, compli- cated and life threatening infections of immunosup- pressed patients [15]. Patients with cystic fibriosis are especially disposed to P. aeruginosa infections and for these persons; the bacterium is responsible for the high rates of morbidity and mortality [16,17]. It can also co- lonize implanted devices, catheters, heart valves or den- tal implants [18]. Using different assays, a broad range of AHLs was detected in cell-free supernatants of bacterial cultures of P. aeruginosa [19-22]. Shaw et al. [23] re- ported the occurrence and separation of 3-hydroxy forms of N-hexanoyl, N-octanoyl, and N-decanoyl-L-homose rine lactones in the supernatant of A. tumefaciens cul- tures with thin layer chromatography. AHLs are the dif- ficult compounds analyzed by the UV detectors as they have absorbance maxima at low wavelength and, coupled with the high background of commonly used solvents [24]. Moreover, these molecules are produced at very low concentrations, so the conventional techniques cannot be used. For this reason, Charlton et al. reported a GC/MS method for the quantification of 3-oxo AHLs based on their derivatization with pentafluorobenzyloxime derivatives [25]. The capillary separation techniques were also developed in conjunction with mass spectrometric detection for the analysis of AHLs from small sample vo- lumes in Burk- holderia cepacia [27-29]. Analyses of N-acyl-L-homoserine lactone in some gramnegative bac-

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<p>Quorum quenching activity of <em>Bacillus cereus</em> isolate 30b confers antipathogenic effects in <em>Pseudomonas aeruginosa</em></p>

<p>Quorum quenching activity of <em>Bacillus cereus</em> isolate 30b confers antipathogenic effects in <em>Pseudomonas aeruginosa</em></p>

Materials and methods: Soil bacteria were screened for aiiA gene coding for lactonase enzyme by Polymerase Chain reaction and sequencing of aiiA gene homologs. Lactonase activity and spectrum were assessed in the cell-free lysate by well diffusion assay using Agrobacterium tumafaciens KYC55. A bacterial isolate showing the highest N-acyl-homoserine lactones degra- dation percentage was identi fi ed by gene ampli fi cation and sequencing of the 16S rRNA gene and its aiiA gene homolog. High performance liquid chromatography was used to con fi rm N-acyl-homoserine lactone degradation. The effect of cell-free lysate on the bio fi lm formation ability and cytotoxicity of P. aeruginosa PAO1 and P. aeruginosa clinical isolates from different clinical sources were assessed by static microtiter plate and viability assay, respectively Results: Lactonase gene and activity were identi fi ed in three Bacillus spp. isolates. They showed broad catalytic activities against tested N-acyl-homoserine lactones. However, The lactonase activity in the cell- free lysate of isolate 30b showed the highest signi fi cant degradation percentage on all tested signals; N-butanoyl-L-homoserine lactone (71%), N-hexanoyl-

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The roles of small RNAs: insights from bacterial quorum sensing

The roles of small RNAs: insights from bacterial quorum sensing

Nonetheless, the functional group (usually fatty acid) ensures the specie-specificity [41] of quorum sensing. Majority of the gram-negative bacteria quorum sensing is regulated by highly conserved LuxR/LuxI family [48] although there are bacteria species like V. harveyi, Staphylococcus aureus and Bacillus subtilis which use two-component systems [42, 49, 50, 51]. Generally speaking, in gram-negative bacteria, LuxI synthases syn- thesise acyl homoserine lactone (AHL) and they diffuse outside the cells [41, 52–54]. AHL molecules diffuse into other cells freely and bind to LuxR receptors in other cells. LuxR protein molecules consist of two domains for DNA binding and autoinducer binding respectively [54]. DNA binding domain is only activated once the autoin- ducers bind [53]. AHL-bound-LuxR protein complex

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6α Acet­oxy­vouacapan 7β,17β lactone

6α Acet­oxy­vouacapan 7β,17β lactone

is observed in ADV (Ruggiero et al., 1997), and its amide (Branco et al., 1999) and lactone derivatives (AbrahaÄo JuÂnior et al., 1997, 2004). As in the 6-hydroxyvouacapan-7,17- lactone compound (AbrahaÄo-Junior et al., 1997), the lactone ring is in an envelope conformation, while the furan ring is planar, with an r.m.s. deviation of ®tted atoms of 0.002 AÊ.

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De­hydro­brachylaenolide: an eudesmane type sesquiterpene lactone

De­hydro­brachylaenolide: an eudesmane type sesquiterpene lactone

The molecular geometry and labelling scheme are shown in Fig. 1. The methylenecyclohexenone ring adopts an envelope conformation, with the C5 atom out of the plane of the ring by approximately 0.7 Å. The γ-lactone ring is twisted on C6—C7, while the cyclohexane ring adopts a chair conformation. An axial position is occupied by methyl group C14, and the methylene carbon atom C15 is in the equatorial position. A weak intramolecular interaction is formed between C15—H15B···O2. Fig. 2 illustrates the molecular packing viewed down the c axis. Weak intermolecular hydrogen bonds are present between atoms C6—H6···O1 i and and C14—H14···O1 i [symmetry code (i): 1/2 - x, 1 - y, 1/2

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3 De­­oxy D galactono 1,4 lactone (3 de­­oxy D xylo hexono 1,4 lactone)

3 De­­oxy D galactono 1,4 lactone (3 de­­oxy D xylo hexono 1,4 lactone)

Lactone (1) can be readily obtained and has a great potential as a chiral building block for the synthesis of complex highly functionalized targets. It has already been used for the synthesis of carnitine (Bols et al., 1992) and hydroxy- lated azepanes (Anderson et al., 2000); it can also prove useful for synthesis of bulgecinines and other highly substituted prolines and pyrrolidines.

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Fungal Homoserine Kinase (thr1Δ) Mutants Are Attenuated in Virulence and Die Rapidly upon Threonine Starvation and Serum Incubation

Fungal Homoserine Kinase (thr1Δ) Mutants Are Attenuated in Virulence and Die Rapidly upon Threonine Starvation and Serum Incubation

droxyaspartic acid or D , L -2-amino-5-phosphonovaleric acid (data not shown). Nonetheless, the rapidity and profound le- thality observed upon exposure of thr1 ⌬ and thr4 ⌬ mutants to serum and threonine starvation conditions indicate that Thr1p and Thr4p inhibitors would be fungicidal in vivo. Such a fun- gicidal effect would be advantageous over fungistatic agents since fungistatic agents require immune function to clear ex- isting fungi from the body so that the infection does not re- crudesce upon drug removal, and many fungal infections occur in immunocompromised individuals. Since both S. cerevisiae and C. albicans thr1 ⌬ are sensitive to other inhibitors of amino acid biosynthesis, likely due to general control-mediated in- creased flux through the threonine biosynthetic pathway that results in increased homoserine production (33), we predict that inhibitors of Thr1p (and Thr4p) would have a therapeu- tically beneficial synergistic action with inhibitors of other amino acid biosynthetic pathways. For example, thr1 ⌬ mutants are hypersensitive to the herbicide sulfometuron methyl (33), which targets the isoleucine and valine biosynthetic enzyme acetolactate synthase, also an interesting drug target, since it is also required for fungal virulence and/or survival in vivo (31, 32, 36). An additional virtue for targeting Thr1p and Thr4p is the demonstration that thr1 ⌬ and thr4 ⌬ mutants are hypersen- sitive to the clinically relevant drug 5-fluorocytosine, even un- der conditions of high threonine. Since 5-fluorocytosine is con- verted into 5-fluorouracil, which inhibits RNA and DNA metabolism (25, 28, 29, 53), and thr1 ⌬ mutants are hypersen- sitive to DNA-damaging agents (2, 3), 5-fluorocytosine-in- duced DNA damage may explain the observed hypersensitivity. Thus, novel Thr1p or Thr4p inhibitors would have great po- tential as sole (C. neoformans) and combination (C. albicans) therapies.

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Dynamic metabolic profiling in vegetable soybean seed development

Dynamic metabolic profiling in vegetable soybean seed development

and DAF67, suggesting that a large portion of new metabolites were synthesized after DAF61. The score plot of PCA for the first two components (R2X =0.810, Q2 0.485) showed a separate trend for the vegetable soybean seeds at the developmental stages (Fig. 1). The first two principal components (PCs) explained 52.5% of the total variance, which PC1 and PC2 accounted for 38.1% and 14.4%, respectively. The metabolites in vegetable soybean seeds which contributed to PC1 was dominated by amino acids (e.g. asparagine, homoserine, threonine, alanine, serine, isoleucine, leucine, valine, proline and lysine) and organic acid (e.g. tetronic acid, suberyl glycine, 2,3-dihydroxybutanedioic acid, succinic acid, malic acid and fumaric acid), while glucose, sorbitol, fructose, melibiose, isomaltose and sucrose were the main contributors of PC2 (Fig. 2, File S1). The resulting composition analysis suggests that the amino acids,

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