Xue Y

References (42)

Title : Characterization of Thermotoga maritima Esterase Capable of Hydrolyzing Bis(2-hydroxyethyl) Terephthalate - Feng_2024_J.Agric.Food.Chem__
Author(s) : Feng S , Xue M , Xie F , Zhao H , Xue Y
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : The gene-encoding carboxylesterase (TM1022) from the hyperthermophilic bacterium Thermotoga maritima (T. maritima) was cloned and expressed in Escherichia coli Top10 and BL21 (DE3). Recombinant TM1022 showed the best activity at pH 8.0 and 85 degreesC and retained 57% activity after 8 h cultivation at 90 degreesC. TM1022 exhibited good stability at pH 6.0-9.0, maintaining 53% activity after incubation at pH 10.0 and 37 degreesC for 6 h. The esterase TM1022 exhibited the optimum thermo-alkali stability and k(cat)/K(m) (598.57 +/- 19.97 s(-1)mM(-1)) for pN-C4. TM1022 hydrolyzed poly(ethylene terephthalate) (PET) degradation intermediates, such as bis(2-hydroxyethyl) terephthalate (BHET) and mono(2-hydroxyethyl) terephthalate (MHET). The K(m), k(cat), and k(cat)/K(m) values for BHET were 0.82 +/- 0.01 mM, 2.20 +/- 0.02 s(-1), and 2.67 +/- 0.02 mM(-1) s(-1), respectively; those for MHET were 2.43 +/- 0.07 mM, 0.04 +/- 0.001 s(-1), and 0.02 +/- 0.001 mM(-1) s(-1), respectively. When purified TM1022 was added to the cutinase BhrPETase, hydrolysis of PET from drinking water bottle tops produced pure terephthalic acids (TPA) with 166% higher yield than those obtained after 72 h of incubation with BhrPETase alone as control. The above findings demonstrate that the esterase TM1022 from T. maritima has substantial potential for depolymerizing PET into monomers for reuse.
ESTHER : Feng_2024_J.Agric.Food.Chem__
PubMedSearch : Feng_2024_J.Agric.Food.Chem__
PubMedID: 38753963
Gene_locus related to this paper: 9bact-a0a2h5z9r5 , thema-ESTA

Title : Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer - Wang_2022_BMC.Cancer_22_635
Author(s) : Wang Y , Fang T , Yin X , Zhang L , Zhang X , Zhang D , Zhang Y , Wang X , Wang H , Xue Y
Ref : BMC Cancer , 22 :635 , 2022
Abstract : BACKGROUND: The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. METHODS: We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. RESULTS: Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. CONCLUSION: AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC.
ESTHER : Wang_2022_BMC.Cancer_22_635
PubMedSearch : Wang_2022_BMC.Cancer_22_635
PubMedID: 35681154
Gene_locus related to this paper: human-AADAC

Title : Colorimetric Assay for Acetylcholinesterase Activity and Inhibitor Screening Based on Metal-Organic Framework Nanosheets - Wang_2022_Anal.Chem_94_16345
Author(s) : Wang Y , Xue Y , Zhao Q , Wang S , Sun J , Yang X
Ref : Analytical Chemistry , 94 :16345 , 2022
Abstract : Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn(2+) and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal-organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the H(2)O(2)-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy.
ESTHER : Wang_2022_Anal.Chem_94_16345
PubMedSearch : Wang_2022_Anal.Chem_94_16345
PubMedID: 36444539

Title : Sensitivity Differences and Biochemical Characteristics of Laodelphax striatellus (Falln) to Seven Insecticides in Different Areas of Shandong, China - Xue_2022_Insects_13_
Author(s) : Xue Y , Liu C , Liu D , Ding W , Li Z , Cao J , Xia X
Ref : Insects , 13 : , 2022
Abstract : Laodelphax striatellus Fallen is one of the main pests that can severely harm rice, corn, and wheat. Insecticides acting on the nicotinic acetylcholine receptor (nAChR) are the main type of pesticides used for the control of L. striatellus in Shandong Province, a major grain-producing region in China. In this study, the rice seedling dipping method was used to determine the sensitivities of six field L. striatellus populations in Shandong to seven insecticides acting on nAChR. The results showed that all the field populations were sensitive to clothianidin, nitenpyram, and triflumezopyrim, and the Jiaxiang population exhibited the lowest resistance ratio (RR) to imidacloprid, dinotefuran, sulfoxaflor, and thiamethoxam. The Donggang population showed a medium-level resistance to imidacloprid, with the highest RR of 17.48-fold. The Yutai population showed low-level resistance to imidacloprid and thiamethoxam, with RRs of 7.23- and 7.02-fold, respectively. The contents of cytochrome P450 monooxygenase (P450s), carboxylesterase (CarE), and glutathione S-transferase (GST) were the highest in the Donggang population and the lowest in the Jiaxiang population. The P450 gene CYP314A1 and the CarE gene LsCarE12 were highly up-regulated in all populations. No mutations of V62I, R81T, and K265E in the nAChR beta1 subunit were found in any of the populations. These results provide valuable information for the strategies of resistance management of L. striatellus in the field.
ESTHER : Xue_2022_Insects_13_
PubMedSearch : Xue_2022_Insects_13_
PubMedID: 36135481

Title : Chemical modification for improving catalytic performance of lipase B from Candida antarctica with hydrophobic proline ionic liquid - Zhang_2022_Bioprocess.Biosyst.Eng_45_749
Author(s) : Zhang XG , Xue Y , Lu ZP , Xu HJ , Hu Y
Ref : Bioprocess Biosyst Eng , 45 :749 , 2022
Abstract : In this study, a series of proline ionic liquids with different lengths of hydrophobic alkyl on the side chain were used to modify the Candida Antarctic lipase B (CALB). The catalytic activity, thermal stability and tolerance to methanol and DMSO of the modified enzyme were all improved simultaneously. The optimum temperature changed from 55 to 60 degC. The hydrophobicity and anion type of the modifier have important influence on the catalytic performance of CALB. CALB modified by [ProC(12)][H(2)PO(4)] has a better effect. Under the optimal conditions, its hydrolysis activity was 3.0 times than that of the native enzyme, the catalytic efficiency Kcat/Km improved 2.8 times in aqueous phase, and the tolerance to organic solvent with strong polarity (50% methanol 2 h) was increased by 6.8 times. Fluorescence spectra and circular dichroism (CD) spectroscopy showed that the introduction of ionic liquids changed the microenvironment near the fluorophores of the enzyme protein, the alpha-helix decreased and beta-sheet increased in the secondary structure of the modified enzymes. The root mean square deviation (RMSD), residue root mean square fluctuation (RMSF), radius of gyration (Rg), and solution accessible surface area (SASA) of [ProC(2)][Br]-CALB, [ProC(12)][Br]-CALB and native CALB were obtained for comparison by molecular dynamics simulation. The results of dynamics simulation were in good agreement with enzymology experiment. The introduction of ionic liquids can keep CALB in a better active conformation, and proline ionic liquids with long hydrophobic chains can significantly improve the surface hydrophobicity and overall rigidity of CALB. This research offers a new idea for rapid screening of efficient modifiers and provision of enzymes with high stability and activity for industrial application.
ESTHER : Zhang_2022_Bioprocess.Biosyst.Eng_45_749
PubMedSearch : Zhang_2022_Bioprocess.Biosyst.Eng_45_749
PubMedID: 35113231

Title : Enhancing the Catalytic Performance of Candida antarctica Lipase B by Chemical Modification With Alkylated Betaine Ionic Liquids - Xue_2022_Front.Bioeng.Biotechnol_10_850890
Author(s) : Xue Y , Zhang XG , Lu ZP , Xu C , Xu HJ , Hu Y
Ref : Front Bioeng Biotechnol , 10 :850890 , 2022
Abstract : Various betaine ionic liquids composed of different chain lengths and different anions were designed and synthesized to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity of all modified lipases improved under different temperature and pH conditions, while also exhibiting enhanced thermostability and tolerance to organic solvents. With an increase in ionic liquid chain length, the modification effect was greater. Overall, CALB modified by [BetaineC(16)][H(2)PO(4)] performed best, with the modified CALB enzyme activity increased 3-fold, thermal stability increased 1.5-fold when stored at 70 degreesC for 30 min, with tolerance increased 2.9-fold in 50% DMSO and 2.3-fold in 30% mercaptoethanol. Fluorescence and circular dichroism (CD) spectroscopic analysis showed that the introduction of an ionic liquid caused changes in the microenvironment surrounding some fluorescent groups and the secondary structure of the CALB enzyme protein. In order to establish the enzyme activity and stability change mechanisms of the modified CALB, the structures of CALB modified with [BetaineC(4)][Cl] and [BetaineC(16)][Cl] were constructed, while the reaction mechanisms were studied by molecular dynamics simulations. Results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating that modified CALB has a more stable structure. Root mean square fluctuation (RMSF) calculations showed that the rigidity of modified CALB was enhanced. Solvent accessibility area (SASA) calculations exhibited that both the hydrophilicity and hydrophobicity of the modified enzyme-proteins were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites also increased. Therefore, modified CALB has enhanced structural stability and higher hydrolytic activity.
ESTHER : Xue_2022_Front.Bioeng.Biotechnol_10_850890
PubMedSearch : Xue_2022_Front.Bioeng.Biotechnol_10_850890
PubMedID: 35265607

Title : In Vitro and in Silico Analysis of Phytochemicals From Fallopia dentatoalata as Dual Functional Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease - Wu_2022_Front.Pharmacol_13_905708
Author(s) : Wu Y , Su X , Lu J , Wu M , Yang SY , Mai Y , Deng W , Xue Y
Ref : Front Pharmacol , 13 :905708 , 2022
Abstract : Current studies have found that butyrylcholinesterase (BuChE) replaces the biological function of acetylcholinesterase (AChE) in the late stage of Alzheimer's disease. Species in the genus of Fallopia, rich in polyphenols with diverse chemical structures and significant biological activities, are considered as an important resource for screening natural products to against AD. In this study, thirty-four compounds (1-34) were isolated from Fallopia dentatoalata (Fr. Schm.) Holub, and their inhibitory effects against AChE and BuChE were assessed. Compounds of the phenylpropanoid sucrose ester class emerged as the most promising members of the group, with 31-33 displaying moderate AChE inhibition (IC50 values ranging from 30.6 +/- 4.7 to 56.0 +/- 2.4 microM) and 30-34 showing potential inhibitory effects against BuChE (IC50 values ranging from 2.7 +/- 1.7 to 17.1 +/- 3.4 microM). Tacrine was used as a positive control (IC50: 126.7 +/- 1.1 in AChE and 5.5 +/- 1.7 nM in BuChE). Kinetic analysis highlighted compounds 31 and 32 as non-competitive inhibitors of AChE with Ki values of -30.0 and -34.4 microM, whilst 30-34 were revealed to competitively inhibit BuChE with Ki values ranging from -1.8 to -17.5 microM. Molecular binding studies demonstrated that 30-34 bound to the catalytic sites of BuChE with negative binding energies. The strong agreement between both in vitro and in silico studies highlights the phenylpropanoid sucrose esters 30-34 as promising candidates for use in future anti-cholinesterase therapeutics against Alzheimer's disease.
ESTHER : Wu_2022_Front.Pharmacol_13_905708
PubMedSearch : Wu_2022_Front.Pharmacol_13_905708
PubMedID: 35899116

Title : Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120\/ABHD6 - Li_2022_Drug.Des.Devel.Ther_16_3557
Author(s) : Li R , Ye Z , She D , Fang P , Zong G , Hu K , Kong D , Xu W , Li L , Zhou Y , Zhang K , Xue Y
Ref : Drug Des Devel Ther , 16 :3557 , 2022
Abstract : OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.
ESTHER : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedSearch : Li_2022_Drug.Des.Devel.Ther_16_3557
PubMedID: 36238196

Title : Acorenone C: A New Spiro-Sesquiterpene from a Mangrove-Associated Fungus, Pseudofusicoccum sp. J003 - Jia_2021_Front.Chem_9_780304
Author(s) : Jia S , Su X , Yan W , Wu M , Wu Y , Lu J , He X , Ding X , Xue Y
Ref : Front Chem , 9 :780304 , 2021
Abstract : Mangrove-derived endophytes are rich in bioactive secondary metabolites with a variety of biological activities. Recently, a fungus Pseudofusicoccum sp. J003 was first isolated by our research group from mangrove species Sonneratia apetala Buch.-Ham. The subsequent chemical investigation of the methanol extract of the culture broth of this strain has led to the isolation of a new sesquiterpenoid named acorenone C (1), two alkaloids (2-3), four phenolic compounds (4-7), and four steroid derivatives (8-11). The new structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR spectroscopy, and HRESIMS. Its absolute configuration was elucidated by experimental ECD and ECD calculation. The in vitro AChE inhibitory, anti-inflammatory, and cytotoxic activities of the selected compounds were evaluated. The results showed that compound 1 showed mild AChE inhibitory activity, with an inhibition rate of 23.34% at the concentration of 50 microM. Compound 9 exerted a significant inhibitory effect against nitric oxide (NO) production in LPS-stimulated RAW 264.7 mouse macrophages, with an inhibition rate of 72.89% at the concentration of 25 microM, better than that of positive control L-NMMA. Compound 9 also displayed obvious inhibition effects on the growth of two human tumor cell lines, HL-60 and SW480 (inhibition rates 98.68 +/- 0.97% and 60.40 +/- 4.51%, respectively). The antimicrobial activities of the compounds (1-11) against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were also tested; however, none of them showed antimicrobial activities.
ESTHER : Jia_2021_Front.Chem_9_780304
PubMedSearch : Jia_2021_Front.Chem_9_780304
PubMedID: 34900941

Title : Experimental and theoretical evidence of enhanced catalytic performance of lipase B from Candida antarctica acquired by the chemical modification with amino acid ionic liquids - Xu_2021_Mol.Catal_501_111355
Author(s) : Xu C , Suo H , Xue Y , Qin J , Chen H , Hu Y
Ref : Molecular Catalysis , 501 :111355 , 2021
Abstract : Four types of amino acid ionic liquids (AAILs) with chiral structure were used to modify Candida antarctica lipase B (CALB). The results showed that the catalytic activity at different temperatures and pH, thermostability, and tolerance to organic solvents of all modified lipases were improved. The composition and configuration of modifiers have great influence on the catalytic performance of the modified lipases. AAILs composed of l-proline exhibited better modification effect than those containing d-proline. The use of [N-AC-l-Pro] [Cl] led to the highest modification degree (47.92 %) of the lipase, which exhibited the highest hydrolytic activity (430.67 U/g), as well as enhanced thermal stability and tolerance to organic solvents. The structure of CALB was characterized by circular dichroism (CD) and fluorescence spectroscopy. It was found that the introduction of a modifier changes the secondary structure of CALB to a certain extent, and the microenvironment around the fluorescent group changed slightly. The structural stability of CALB modified with [N-AC-l-Pro] [Cl] and the mechanism of reaction were studied by molecular dynamics simulations. The molecular dynamics simulations of the native and modified CALB were performed for 20 ns at 300 and 328 K. The simulation results showed that the root mean square deviation (RMSD) and total energy of modified CALB were less than those of native CALB, indicating a more stable structure for the modified CALB. The root mean square fluctuation (RMSF) calculations showed that the rigidity of the modified CALB and the flexibility of the active center region were both enhanced. The solvent accessibility area (SASA) calculations showed that both hydrophilicity and hydrophobicity of the modified enzyme-protein were improved. The increase in radial distribution function (RDF) of water molecules confirmed that the number of water molecules around the active sites was also increased. Thus, the modified CALB has enhanced structural stability and higher hydrolytic activity towards the triglyceride substrates.
ESTHER : Xu_2021_Mol.Catal_501_111355
PubMedSearch : Xu_2021_Mol.Catal_501_111355

Title : Dynamic changes in chemical compositions and anti-acetylcholinesterase activity associated with steaming process of stem-leaf saponins of Panax notoginseng - Ma_2021_Biomed.Chromatogr__e5077
Author(s) : Ma C , Guan H , Lin Q , Liu C , Ju Z , Xue Y , Cheng X , Wang C
Ref : Biomedical Chromatography , :e5077 , 2021
Abstract : Stem-leaf saponins (SLS), the total saponins from aerial part of P. notoginseng, are by-products of notoginseng, a famous tradition Chinese medicine. SLS have been used as a health functional food in China, but its mild effects limited clinical applications in diseases. Inspired by steaming of notoginseng to enhance pharmacological activity, a steaming protocol was developed to deal SLS. SLS were steamed at 100 degreesC, 120 degreesC, and 140 degreesC for 1, 2, 3, and 4 h, respectively. The UPLC-Q-TOF and UPLC-MS/MS were applied to analyze the dynamic changes in chemical compositions. Anti-acetylcholinesterase activity of steamed SLS were assessed in vitro by directly determining the metabolic product of acetylcholine, choline. The components of SLS were significantly changed by steaming. Total 117 saponins and aglycones were characterized, and 35 of them were newly generated. The anti-acetylcholinesterase activity of steamed SLS gradually increased with the extension of steamed time and the increase of steamed temperature and reached the maximum after 140 degreesC for 3 h. Furthermore, ginsenosides Rk1 and Rg5, the main components of steamed SLS, showed dose-dependent anti-acetylcholinesterase activities with IC(50) values of 26.88 +/- 0.53 microM and 22.41 +/- 1.31 microM that were only 1.8- and 1.5-fold higher than donepezil, respectively.
ESTHER : Ma_2021_Biomed.Chromatogr__e5077
PubMedSearch : Ma_2021_Biomed.Chromatogr__e5077
PubMedID: 33475178

Title : Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum - Guo_2018_Org.Biomol.Chem_16_8130
Author(s) : Guo Y , Zhang N , Sun W , Duan X , Zhang Q , Zhou Q , Chen C , Zhu H , Luo Z , Liu J , Li XN , Xue Y , Zhang Y
Ref : Org Biomol Chem , 16 :8130 , 2018
Abstract : Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
ESTHER : Guo_2018_Org.Biomol.Chem_16_8130
PubMedSearch : Guo_2018_Org.Biomol.Chem_16_8130
PubMedID: 30334059

Title : Synergism of antihypertensives and cholinesterase inhibitors in Alzheimer's disease - Hu_2018_Alzheimers.Dement.(N.Y)_4_542
Author(s) : Hu Z , Wang L , Ma S , Kirisci L , Feng Z , Xue Y , Klunk WE , Kamboh MI , Sweet RA , Becker J , Lv Q , Lopez OL , Xie XQ
Ref : Alzheimers Dement (N Y) , 4 :542 , 2018
Abstract : Introduction: We investigated the effect of antihypertensive (aHTN) medications and cholinesterase inhibitors (ChEIs) on the cognitive decline in patients with Alzheimer's disease (AD) and analyzed synergism by chemogenomics systems pharmacology mapping. Methods: We compared the effect of aHTN drugs on Mini-Mental State Examination scores in 617 AD patients with hypertension, and studied the synergistic effects. Results: The combination of diuretics, calcium channel blockers, and renin-angiotensin-aldosterone system blockers showed slower cognitive decline compared with other aHTN groups (Deltabeta = +1.46, P < .0001). aHTN medications slow down cognitive decline in ChEI users (Deltabeta = +0.56, P = .006), but not in non-ChEI users (Deltabeta = -0.31, P = .53). Discussion: aHTN and ChEI drugs showed synergistic effects. A combination of diuretics, renin-angiotensin-aldosterone system blockers, and calcium channel blockers had the slowest cognitive decline. The chemogenomics systems pharmacology-identified molecular targets provide system pharmacology interpretation of the synergism of the drugs in clinics. The results suggest that improving vascular health is essential for AD treatment and provide a novel direction for AD drug development.
ESTHER : Hu_2018_Alzheimers.Dement.(N.Y)_4_542
PubMedSearch : Hu_2018_Alzheimers.Dement.(N.Y)_4_542
PubMedID: 30386819

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract : Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.
ESTHER : Qi_2018_Org.Biomol.Chem_16_9046
PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

Title : Asperversins A and B, Two Novel Meroterpenoids with an Unusual 5\/6\/6\/6 Ring from the Marine-Derived Fungus Aspergillus versicolor - Li_2018_Mar.Drugs_16_
Author(s) : Li H , Sun W , Deng M , Qi C , Chen C , Zhu H , Luo Z , Wang J , Xue Y , Zhang Y
Ref : Mar Drugs , 16 : , 2018
Abstract : Asperversins A (1) and B (2), two novel meroterpenoids featuring an uncommon 5/6/6/6 ring system, along with five new analogues (3(-)7) and a known compound asperdemin (8), were obtained from the marine-derived fungus Aspergillus versicolor. Their structures and absolute configurations were confirmed by extensive spectroscopic analyses, single-crystal X-ray diffraction studies, and electronic circular dichroism (ECD) calculation. All new compounds were tested for their acetylcholinesterase enzyme (AChE) inhibitory activities and cytotoxic activities, of which compound 7 displayed moderate inhibitory activity against the AChE with an IC50 value of 13.6 μM.
ESTHER : Li_2018_Mar.Drugs_16_
PubMedSearch : Li_2018_Mar.Drugs_16_
PubMedID: 29882867

Title : Human Neutralizing Monoclonal Antibody Inhibition of Middle East Respiratory Syndrome Coronavirus Replication in the Common Marmoset - Chen_2017_J.Infect.Dis_215_1807
Author(s) : Chen Z , Bao L , Chen C , Zou T , Xue Y , Li F , Lv Q , Gu S , Gao X , Cui S , Wang J , Qin C , Jin Q
Ref : J Infect Dis , 215 :1807 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) infection in humans is highly lethal, with a fatality rate of 35%. New prophylactic and therapeutic strategies to combat human infections are urgently needed. We isolated a fully human neutralizing antibody, MCA1, from a human survivor. The antibody recognizes the receptor-binding domain of MERS-CoV S glycoprotein and interferes with the interaction between viral S and the human cellular receptor human dipeptidyl peptidase 4 (DPP4). To our knowledge, this study is the first to report a human neutralizing monoclonal antibody that completely inhibits MERS-CoV replication in common marmosets. Monotherapy with MCA1 represents a potential alternative treatment for human infections with MERS-CoV worthy of evaluation in clinical settings.
ESTHER : Chen_2017_J.Infect.Dis_215_1807
PubMedSearch : Chen_2017_J.Infect.Dis_215_1807
PubMedID: 28472421

Title : Methylotrophic yeast Pichia pastoris as a chassis organism for polyketide synthesis via the full citrinin biosynthetic pathway - Xue_2017_J.Biotechnol_242_64
Author(s) : Xue Y , Kong C , Shen W , Bai C , Ren Y , Zhou X , Zhang Y , Cai M
Ref : J Biotechnol , 242 :64 , 2017
Abstract : With the rapid development of synthetic biology, exploring various chassis organisms has become necessary to improve the heterologous biosynthesis of natural products and pharmaceuticals. In this study, we tested the potential of the industrial methylotrophic yeast strain Pichia pastoris for the heterologous synthesis of polyketides. A recombinant P. pastoris GS-pksCT-npgA carrying the Monascus purpureus citrinin polyketide synthase gene pksCT and the Aspergillus nidulans phosphopantetheinyl transferase gene npgA was constructed. Subsequently, a specific compound was isolated and identified as citrinin intermediate trimethylated pentaketide aldehyde. On account of the hypothetic functions of the genes in the citrinin gene cluster, mpl1 encoding serine hydrolase, mpl2 encoding oxygenase, and mpl4 encoding dehydrogenase were gradually expressed. Proteins were also normally expressed, but a new compound was undetected. Basing on the recently reported citrinin gene cluster in Monascus ruber, we obtained two other genes (mpl6 and mpl7) participating in citrinin biosynthesis by genome walking in M. purpureus. Then, we co-transformed intron-removed mpl6 and mpl7 into the P. pastoris strain carrying pksCT, npgA, mpl1, mpl2, and mpl4. All genes were activated by the methanol-induced AOX1 promoter, and a complete biosynthetic pathway of citrinin was assembled. Finally, citrinin was successfully produced under methanol induction in P. pastoris. These results prove that P. pastoris is a promising chassis organism for polyketide production.
ESTHER : Xue_2017_J.Biotechnol_242_64
PubMedSearch : Xue_2017_J.Biotechnol_242_64
PubMedID: 27913218
Gene_locus related to this paper: monpu-cita

Title : Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum perforatum - Guo_2017_J.Nat.Prod_80_1493
Author(s) : Guo Y , Zhang N , Chen C , Huang J , Li XN , Liu J , Zhu H , Tong Q , Zhang J , Luo Z , Xue Y , Zhang Y
Ref : Journal of Natural Products , 80 :1493 , 2017
Abstract : The new polyprenylated acylphloroglucinol derivatives 1-15 and the known furohyperforin (16) were isolated from the stems and leaves of Hypericum perforatum. Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G (10) and H (11) are similarly the first examples of naturally occurring [3.3.1]-type polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory activities and cytotoxic activities against a panel of human tumor cell lines. Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC50 3.98-9.13 muM) against AChE.
ESTHER : Guo_2017_J.Nat.Prod_80_1493
PubMedSearch : Guo_2017_J.Nat.Prod_80_1493
PubMedID: 28445039

Title : Galanthamine, Plicamine, and Secoplicamine Alkaloids from Zephyranthes candida and Their Anti-acetylcholinesterase and Anti-inflammatory Activities - Zhan_2016_J.Nat.Prod_79_760
Author(s) : Zhan G , Zhou J , Liu R , Liu T , Guo G , Wang J , Xiang M , Xue Y , Luo Z , Zhang Y , Yao G
Ref : Journal of Natural Products , 79 :760 , 2016
Abstract : Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 muM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 muM.
ESTHER : Zhan_2016_J.Nat.Prod_79_760
PubMedSearch : Zhan_2016_J.Nat.Prod_79_760
PubMedID: 26913788

Title : Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure-Based Hit Evaluation and Chemistry Exploration - Xue_2016_ChemMedChem_11_497
Author(s) : Xue Y , Olsson T , Johansson CA , Oster L , Beisel HG , Rohman M , Karis D , Backstrom S
Ref : ChemMedChem , 11 :497 , 2016
Abstract : Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series.
ESTHER : Xue_2016_ChemMedChem_11_497
PubMedSearch : Xue_2016_ChemMedChem_11_497
PubMedID: 26845235
Gene_locus related to this paper: human-EPHX2

Title : Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine - Zhou_2016_Lipids.Health.Dis_15_135
Author(s) : Zhou MM , Xue Y , Sun SH , Wen M , Li ZJ , Xu J , Wang JF , Yanagita T , Wang YM , Xue CH
Ref : Lipids Health Dis , 15 :135 , 2016
Abstract : BACKGROUND: Phosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti-aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress.
METHODS: Male BALB/c mice were randomly divided into 5 groups: model (M) group, control (Con) group, egg yolk lecithin (EL) group, squid PC (SQ-PC) group and sea cucumber PC (SC-PC) group. The intraperitoneal injection of scopolamine hydrobromide (5 mg/kg) was carried out on the 8(th) of group feeding and sustained daily until the end of test. Morris water maze test was used to evaluate the improvement of cognitive decline and the activity of acetylcholinesterase (AchE), superoxide dismutase (SOD) and monoamine oxidase (MAO) and malondialdehyde (MDA) content in brain were measured to assess the physiological changes.
RESULTS: In behavior test, the latency of PC groups was significantly reduced, while number of crossing the platform and time in target quadrant were increased in comparison with M group and the improvements of SQ-PC and SC-PC were better than that of EL (P < 0.05). Similar trend was observed in physiological changes. The AchE activity was effectively decreased and the SOD activity increased in hippocampus, cortex and white matter when comparing PC groups with M group. SQ-PC, SC-PC and EL respectively showed 22.82, 28.80 and 11.81 % decrease in MDA level in brain compared with M group. The MAO activity in white matter of SQ-PC, SC-PC and EL group separately depressed 33.05, 33.64 and 19.73 % in comparison with M group. No significance between SQ-PC and SC-PC was found in these indicators except the SOD activity in hippocampus and white matter. SQ-PC group had a higher SOD activity in hippocampus (103.68U/mg . prot.) and lower in white matter (120.57 U/mg . prot.) than SC-PC group (95.53 U/mg . prot. in hippocampus, 134.49 U/mg . prot. in white matter). PC rich in n-3 PUFA acted more ameliorative effects than that barely contained on the indicators above.
CONCLUSIONS: Different fatty acids composition of PC all could diminish the cognitive decline and biological damage and protect the brain. EPA and DHA partly enhaced to the advantageous effects.
ESTHER : Zhou_2016_Lipids.Health.Dis_15_135
PubMedSearch : Zhou_2016_Lipids.Health.Dis_15_135
PubMedID: 27558491

Title : Successful generation of structural information for fragment-based drug discovery - Oster_2015_Drug.Discov.Today_20_1104
Author(s) : Oster L , Tapani S , Xue Y , Kack H
Ref : Drug Discov Today , 20 :1104 , 2015
Abstract : Fragment-based drug discovery relies upon structural information for efficient compound progression, yet it is often challenging to generate structures with bound fragments. A summary of recent literature reveals that a wide repertoire of experimental procedures is employed to generate ligand-bound crystal structures successfully. We share in-house experience from setting up and executing fragment crystallography in a project that resulted in 55 complex structures. The ligands span five orders of magnitude in affinity and the resulting structures are made available to be of use, for example, for development of computational methods. Analysis of the results revealed that ligand properties such as potency, ligand efficiency (LE) and, to some degree, clogP influence the success of complex structure generation.
ESTHER : Oster_2015_Drug.Discov.Today_20_1104
PubMedSearch : Oster_2015_Drug.Discov.Today_20_1104
PubMedID: 25931264
Gene_locus related to this paper: human-EPHX2

Title : Whole Genome Sequence of the Probiotic Strain Lactobacillus paracasei N1115, Isolated from Traditional Chinese Fermented Milk - Wang_2014_Genome.Announc_2_e00059
Author(s) : Wang S , Zhu H , He F , Luo Y , Kang Z , Lu C , Feng L , Lu X , Xue Y , Wang H
Ref : Genome Announc , 2 : , 2014
Abstract : Lactobacillus paracasei N1115 is a new strain with probiotic properties isolated from traditional homemade dairy products in Inner Mongolia, China. Here, we report the complete genome sequence of L. paracasei N1115, which shows high similarity to the well-studied probiotic Lactobacillus rhamnosus GG, and 3 structures turned out to be inversions, according to the colinearity analysis of the BLAST alignment.
ESTHER : Wang_2014_Genome.Announc_2_e00059
PubMedSearch : Wang_2014_Genome.Announc_2_e00059
PubMedID: 24625864
Gene_locus related to this paper: lacc3-q03b36 , lacrh-pepr , lacca-b5qt93 , lacca-k0n1x0 , lacpa-s2ter8 , lacpa-s2rz88

Title : A novel alkaliphilic bacillus esterase belongs to the 13(th) bacterial lipolytic enzyme family - Rao_2013_PLoS.One_8_e60645
Author(s) : Rao L , Xue Y , Zheng Y , Lu JR , Ma Y
Ref : PLoS ONE , 8 :e60645 , 2013
Abstract : BACKGROUND: Microbial derived lipolytic hydrolysts are an important class of biocatalysts because of their huge abundance and ability to display bioactivities under extreme conditions. In spite of recent advances, our understanding of these enzymes remains rudimentary. The aim of our research is to advance our understanding by seeking for more unusual lipid hydrolysts and revealing their molecular structure and bioactivities. METHODOLOGYPRINCIPAL FINDINGS: Bacillus. pseudofirmus OF4 is an extreme alkaliphile with tolerance of pH up to 11. In this work we successfully undertook a heterologous expression of a gene estof4 from the alkaliphilic B. pseudofirmus sp OF4. The recombinant protein called EstOF4 was purified into a homologous product by Ni-NTA affinity and gel filtration. The purified EstOF4 was active as dimer with the molecular weight of 64 KDa. It hydrolyzed a wide range of substrates including p-nitrophenyl esters (C2-C12) and triglycerides (C2-C6). Its optimal performance occurred at pH 8.5 and 50 degrees C towards p-nitrophenyl caproate and triacetin. Sequence alignment revealed that EstOF4 shared 71% identity to esterase Est30 from Geobacillus stearothermophilus with a typical lipase pentapeptide motif G91LS93LG95. A structural model developed from homology modeling revealed that EstOF4 possessed a typical esterase 6alpha/7beta hydrolase fold and a cap domain. Site-directed mutagenesis and inhibition studies confirmed the putative catalytic triad Ser93, Asp190 and His220. CONCLUSION: EstOF4 is a new bacterial esterase with a preference to short chain ester substrates. With a high sequence identity towards esterase Est30 and several others, EstOF4 was classified into the same bacterial lipolytic family, Family XIII. All the members in this family originate from the same bacterial genus, bacillus and display optimal activities from neutral pH to alkaline conditions with short and middle chain length substrates. However, with roughly 70% sequence identity, these enzymes showed hugely different thermal stabilities, indicating their diverse thermal adaptations via just changing a few amino acid residues.
ESTHER : Rao_2013_PLoS.One_8_e60645
PubMedSearch : Rao_2013_PLoS.One_8_e60645
PubMedID: 23577139

Title : Insights into hominid evolution from the gorilla genome sequence - Scally_2012_Nature_483_169
Author(s) : Scally A , Dutheil JY , Hillier LW , Jordan GE , Goodhead I , Herrero J , Hobolth A , Lappalainen T , Mailund T , Marques-Bonet T , McCarthy S , Montgomery SH , Schwalie PC , Tang YA , Ward MC , Xue Y , Yngvadottir B , Alkan C , Andersen LN , Ayub Q , Ball EV , Beal K , Bradley BJ , Chen Y , Clee CM , Fitzgerald S , Graves TA , Gu Y , Heath P , Heger A , Karakoc E , Kolb-Kokocinski A , Laird GK , Lunter G , Meader S , Mort M , Mullikin JC , Munch K , O'Connor TD , Phillips AD , Prado-Martinez J , Rogers AS , Sajjadian S , Schmidt D , Shaw K , Simpson JT , Stenson PD , Turner DJ , Vigilant L , Vilella AJ , Whitener W , Zhu B , Cooper DN , de Jong P , Dermitzakis ET , Eichler EE , Flicek P , Goldman N , Mundy NI , Ning Z , Odom DT , Ponting CP , Quail MA , Ryder OA , Searle SM , Warren WC , Wilson RK , Schierup MH , Rogers J , Tyler-Smith C , Durbin R
Ref : Nature , 483 :169 , 2012
Abstract : Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution.
ESTHER : Scally_2012_Nature_483_169
PubMedSearch : Scally_2012_Nature_483_169
PubMedID: 22398555
Gene_locus related to this paper: gorgo-g3qfr8 , gorgo-g3qgi3 , gorgo-g3r1s1 , gorgo-g3r9p9 , gorgo-a0a2i2zrx6 , gorgo-g3re16 , gorgo-g3s122 , gorgo-a0a2i2y3x8

Title : A thermostable esterase from Thermoanaerobacter tengcongensis opening up a new family of bacterial lipolytic enzymes - Rao_2011_Biochim.Biophys.Acta_1814_1695
Author(s) : Rao L , Xue Y , Zhou C , Tao J , Li G , Lu JR , Ma Y
Ref : Biochimica & Biophysica Acta , 1814 :1695 , 2011
Abstract : An unidentified alpha/beta hydrolase gene lipA3 from thermostable eubacterium species Thermoanaerobacter tengcongensis MB4 was cloned and heterologously expressed by Escherichia coli BL21(DE3)pLysS. The purified recombinant enzyme EstA3 turned out to be a monomeric thermostable esterase with optimal activity at 70degC and pH 9.5. The enzyme showed lipolytic activity towards a wide range of ester substrates including p-nitrophenyl esters and triacylglycerides, with the highest activity being observed for p-nitrophenyl caproate at 150 U/mg and for Triacetin at 126U/mg, respectively. Phylogenetic analysis revealed that EstA3 did not show homology to any identified bacterial lipolytic hydrolases. Sequence alignment showed that there was a common pentapeptide CHSMG with a cysteine replacing the first glycine in most esterase and lipase conserved motif GXSXG. The catalytic triad of EstA3 is Ser92, Asp269 and His292, which was confirmed by site directed mutagenesis. Based on the enzymatic properties and sequence alignment we concluded that the esterase EstA3 represented a novel bacterial lipolytic enzyme group and in chronological order this group was assigned as Family XIV.
ESTHER : Rao_2011_Biochim.Biophys.Acta_1814_1695
PubMedSearch : Rao_2011_Biochim.Biophys.Acta_1814_1695
PubMedID: 21907313
Gene_locus related to this paper: thete-LIPA3

Title : Genome of alkaliphilic Bacillus pseudofirmus OF4 reveals adaptations that support the ability to grow in an external pH range from 7.5 to 11.4 - Janto_2011_Environ.Microbiol_13_3289
Author(s) : Janto B , Ahmed A , Ito M , Liu J , Hicks DB , Pagni S , Fackelmayer OJ , Smith TA , Earl J , Elbourne LD , Hassan K , Paulsen IT , Kolsto AB , Tourasse NJ , Ehrlich GD , Boissy R , Ivey DM , Li G , Xue Y , Ma Y , Hu FZ , Krulwich TA
Ref : Environ Microbiol , 13 :3289 , 2011
Abstract : Bacillus pseudofirmus OF4 is an extreme but facultative alkaliphile that grows non-fermentatively in a pH range from 7.5 to above 11.4 and can withstand large sudden increases in external pH. It is a model organism for studies of bioenergetics at high pH, at which energy demands are higher than at neutral pH because both cytoplasmic pH homeostasis and ATP synthesis require more energy. The alkaliphile also tolerates a cytoplasmic pH>9.0 at external pH values at which the pH homeostasis capacity is exceeded, and manages other stresses that are exacerbated at alkaline pH, e.g. sodium, oxidative and cell wall stresses. The genome of B.pseudofirmus OF4 includes two plasmids that are lost from some mutants without viability loss. The plasmids may provide a reservoir of mobile elements that promote adaptive chromosomal rearrangements under particular environmental conditions. The genome also reveals a more acidic pI profile for proteins exposed on the outer surface than found in neutralophiles. A large array of transporters and regulatory genes are predicted to protect the alkaliphile from its overlapping stresses. In addition, unanticipated metabolic versatility was observed, which could ensure requisite energy for alkaliphily under diverse conditions.
ESTHER : Janto_2011_Environ.Microbiol_13_3289
PubMedSearch : Janto_2011_Environ.Microbiol_13_3289
PubMedID: 21951522
Gene_locus related to this paper: alkpo-d3fst0

Title : Prediction of acetylcholinesterase inhibitors and characterization of correlative molecular descriptors by machine learning methods - Lv_2010_Eur.J.Med.Chem_45_1167
Author(s) : Lv W , Xue Y
Ref : Eur Journal of Medicinal Chemistry , 45 :1167 , 2010
Abstract : Acetylcholinesterase (AChE) has become an important drug target and its inhibitors have proved useful in the symptomatic treatment of Alzheimer's disease. This work explores several machine learning methods (support vector machine (SVM), k-nearest neighbor (k-NN), and C4.5 decision tree (C4.5 DT)) for predicting AChE inhibitors (AChEIs). A feature selection method is used for improving prediction accuracy and selecting molecular descriptors responsible for distinguishing AChEIs and non-AChEIs. The prediction accuracies are 76.3% approximately 88.0% for AChEIs and 74.3% approximately 79.6% for non-AChEIs based on the three kinds of machine learning methods. This work suggests that machine learning methods such as SVM are facilitating for predicting AChEIs potential of unknown sets of compounds and for exhibiting the molecular descriptors associated with AChEIs.
ESTHER : Lv_2010_Eur.J.Med.Chem_45_1167
PubMedSearch : Lv_2010_Eur.J.Med.Chem_45_1167
PubMedID: 20053484

Title : Complete genome sequence of the extremophilic Bacillus cereus strain Q1 with industrial applications - Xiong_2009_J.Bacteriol_191_1120
Author(s) : Xiong Z , Jiang Y , Qi D , Lu H , Yang F , Yang J , Chen L , Sun L , Xu X , Xue Y , Zhu Y , Jin Q
Ref : Journal of Bacteriology , 191 :1120 , 2009
Abstract : Bacillus cereus strain Q1 was isolated from a deep-subsurface oil reservoir in the Daqing oil field in northeastern China. This strain is able to produce biosurfactants and to survive in extreme environments. Here we report the finished and annotated genome sequence of this organism.
ESTHER : Xiong_2009_J.Bacteriol_191_1120
PubMedSearch : Xiong_2009_J.Bacteriol_191_1120
PubMedID: 19060151
Gene_locus related to this paper: bacah-a0rer5 , bacan-BA0954 , bacan-BA3703 , bacan-BA4338 , bacan-BA5009 , bacan-DHBF , bacc1-q73br9 , bacce-BC0192 , bacce-BC0968 , bacce-BC1788 , bacce-BC2141 , bacce-BC2171 , bacce-BC4102 , bacce-BC4854 , bacce-BC4862 , bacce-BC5130 , bacce-c2mr40 , bacce-PHAC , bacce-q72yu1 , bacce-q736x9 , baccq-b9j170 , baccr-pepx , baccz-q636u4 , bacti-q3elq7

Title : A putative lipase gene EXTRA GLUME1 regulates both empty-glume fate and spikelet development in rice - Li_2009_Plant.J_57_593
Author(s) : Li H , Xue D , Gao Z , Yan M , Xu W , Xing Z , Huang D , Qian Q , Xue Y
Ref : Plant J , 57 :593 , 2009
Abstract : Recent studies have shown that molecular control of inner floral organ identity appears to be largely conserved between monocots and dicots, but little is known regarding the molecular mechanism underlying development of the monocot outer floral organ, a unique floral structure in grasses. In this study, we report the cloning of the rice EXTRA GLUME1 (EG1) gene, a putative lipase gene that specifies empty-glume fate and floral meristem determinacy. In addition to affecting the identity and number of empty glumes, mutations in EG1 caused ectopic floral organs to be formed at each organ whorl or in extra ectopic whorls. Iterative glume-like structures or new floral organ primordia were formed in the presumptive region of the carpel, resulting in an indeterminate floral meristem. EG1 is expressed strongly in inflorescence primordia and weakly in developing floral primordia. We also found that the floral meristem and organ identity gene OsLHS1 showed altered expression with respect to both pattern and levels in the eg1 mutant, and is probably responsible for the pleiotropic floral defects in eg1. As a putative class III lipase that functionally differs from any known plant lipase, EG1 reveals a novel pathway that regulates rice empty-glume fate and spikelet development.
ESTHER : Li_2009_Plant.J_57_593
PubMedSearch : Li_2009_Plant.J_57_593
PubMedID: 18980657

Title : Tobacco\/nicotine and endogenous brain opioids - Xue_2008_Prog.Neuropsychopharmacol.Biol.Psychiatry_32_1131
Author(s) : Xue Y , Domino EF
Ref : Prog Neuropsychopharmacol Biological Psychiatry , 32 :1131 , 2008
Abstract : Smoking is a major public health problem with devastating health consequences. Although many cigarette smokers are able to quit, equal numbers of others cannot! Standard medications to assist in smoking cessation, such as nicotine replacement therapies and bupropion, are ineffective in many remaining smokers. Recent developments in the neurobiology of nicotine dependence have identified several neurotransmitter systems that may contribute to the process of smoking maintenance and relapse. These include: especially dopamine, but also norepinephrine, 5-hydroxytryptamine, acetylcholine, endogenous opioids, gamma-aminobutyric acid (GABA), glutamate, and endocannabinoids. The present review examines the limited contribution of the endogenous opioid system to the complex effects of nicotine/tobacco smoking.
ESTHER : Xue_2008_Prog.Neuropsychopharmacol.Biol.Psychiatry_32_1131
PubMedSearch : Xue_2008_Prog.Neuropsychopharmacol.Biol.Psychiatry_32_1131
PubMedID: 18215788

Title : Stability and activity of lipase in subcritical 1,1,1,2-tetrafluoroethane (R134a) - Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
Author(s) : Yu G , Xue Y , Xu W , Zhang J , Xue CH
Ref : J Ind Microbiol Biotechnol , 34 :793 , 2007
Abstract : The stability and activity of commercial immobilized lipase from Candida antarctica (Novozym 435) in subcritical 1,1,1,2-tetrafluoroethane (R134a) was investigated. The esterification of oleic acid with glycerol was studied as a model reaction in subcritical R134a and in solvent-free conditions. The results indicated that subcritical R134a treatment led to significant increase of activity of Novozym 435, and a maximum residual activity of 300% was measured at 4 MPa, 30 degrees C after 7 h incubation. No deactivation of Novozym 435 treated with subcritical R134a under different operation factors (pressure 2-8 MPa, temperature 30-60 degrees C, incubation time 1-12 h, water content 1:1, 1:2, 1:5 enzyme/water, depressurization rate 4 MPa/1 min, 4 MPa/30 min, 4 MPa/90 min) was observed. While the initial reaction rate was high in subcritical R134a, higher conversion was obtained in solvent-free conditions. Though the apparent conversion of the reaction is lower in subcritical R134a, it is more practicable, especially at low enzyme concentrations desired at commercial scales.
ESTHER : Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
PubMedSearch : Yu_2007_J.Ind.Microbiol.Biotechnol_34_793
PubMedID: 17909872

Title : Proteomic analyses of Oryza sativa mature pollen reveal novel proteins associated with pollen germination and tube growth - Dai_2006_Proteomics_6_2504
Author(s) : Dai S , Li L , Chen T , Chong K , Xue Y , Wang T
Ref : Proteomics , 6 :2504 , 2006
Abstract : As a highly reduced organism, pollen performs specialized functions to generate and carry sperm into the ovule by its polarily growing pollen tube. Yet the molecular genetic basis of these functions is poorly understood. Here, we identified 322 unique proteins, most of which were not reported previously to be in pollen, from mature pollen of Oryza sativa L. ssp japonica using a proteomic approach, 23% of them having more than one isoform. Functional classification reveals that an overrepresentation of the proteins was related to signal transduction (10%), wall remodeling and metabolism (11%), and protein synthesis, assembly and degradation (14%), as well as carbohydrate and energy metabolism (25%). Further, 11% of the identified proteins are functionally unknown and do not contain any conserved domain associated with known activities. These analyses also identified 5 novel proteins by de novo sequencing and revealed several important proteins, mainly involved in signal transduction (such as protein kinases, receptor kinase-interacting proteins, guanosine 5'-diphosphate dissociation inhibitors, C2 domain-containing proteins, cyclophilins), protein synthesis, assembly and degradation (such as prohibitin, mitochondrial processing peptidase, putative UFD1, AAA+ ATPase), and wall remodeling and metabolism (such as reversibly glycosylated polypeptides, cellulose synthase-like OsCsLF7). The study is the first close investigation, to our knowledge, of protein complement in mature pollen, and presents useful molecular information at the protein level to further understand the mechanisms underlying pollen germination and tube growth.
ESTHER : Dai_2006_Proteomics_6_2504
PubMedSearch : Dai_2006_Proteomics_6_2504
PubMedID: 16548068

Title : Complete genome sequence of Shigella flexneri 5b and comparison with Shigella flexneri 2a - Nie_2006_BMC.Genomics_7_173
Author(s) : Nie H , Yang F , Zhang X , Yang J , Chen L , Wang J , Xiong Z , Peng J , Sun L , Dong J , Xue Y , Xu X , Chen S , Yao Z , Shen Y , Jin Q
Ref : BMC Genomics , 7 :173 , 2006
Abstract : BACKGROUND: Shigella bacteria cause dysentery, which remains a significant threat to public health. Shigella flexneri is the most common species in both developing and developed countries. Five Shigella genomes have been sequenced, revealing dynamic and diverse features. To investigate the intra-species diversity of S. flexneri genomes further, we have sequenced the complete genome of S. flexneri 5b strain 8401 (abbreviated Sf8401) and compared it with S. flexneri 2a (Sf301).
RESULTS: The Sf8401 chromosome is 4.5-Mb in size, a little smaller than that of Sf301, mainly because the former lacks the SHI-1 pathogenicity island (PAI). Compared with Sf301, there are 6 inversions and one translocation in Sf8401, which are probably mediated by insertion sequences (IS). There are clear differences in the known PAIs between these two genomes. The bacteriophage SfV segment remaining in SHI-O of Sf8401 is clearly larger than the remnants of bacteriophage SfII in Sf301. SHI-1 is absent from Sf8401 but a specific related protein is found next to the pheV locus. SHI-2 is involved in one intra-replichore inversion near the origin of replication, which may change the expression of iut/iuc genes. Moreover, genes related to the glycine-betaine biosynthesis pathway are present only in Sf8401 among the known Shigella genomes. CONCLUSION: Our data show that the two S. flexneri genomes are very similar, which suggests a high level of structural and functional conservation between the two serotypes. The differences reflect different selection pressures during evolution. The ancestor of S. flexneri probably acquired SHI-1 and SHI-2 before SHI-O was integrated and the serotypes diverged. SHI-1 was subsequently deleted from the S. flexneri 5b genome by recombination, but stabilized in the S. flexneri 2a genome. These events may have contributed to the differences in pathogenicity and epidemicity between the two serotypes of S. flexneri.
ESTHER : Nie_2006_BMC.Genomics_7_173
PubMedSearch : Nie_2006_BMC.Genomics_7_173
PubMedID: 16822325
Gene_locus related to this paper: shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PTRB , shifl-S2753 , shifl-SF1808 , shifl-SF3046 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH , shiss-yeiG , shiss-yqia

Title : Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery - Yang_2005_Nucleic.Acids.Res_33_6445
Author(s) : Yang F , Yang J , Zhang X , Chen L , Jiang Y , Yan Y , Tang X , Wang J , Xiong Z , Dong J , Xue Y , Zhu Y , Xu X , Sun L , Chen S , Nie H , Peng J , Xu J , Wang Y , Yuan Z , Wen Y , Yao Z , Shen Y , Qiang B , Hou Y , Yu J , Jin Q
Ref : Nucleic Acids Research , 33 :6445 , 2005
Abstract : The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300 approximately 700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
ESTHER : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedSearch : Yang_2005_Nucleic.Acids.Res_33_6445
PubMedID: 16275786
Gene_locus related to this paper: ecoli-yeiG , shidy-IROD , shidy-q67dv1 , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-S2753 , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YJFP , shifl-YPFH , shiss-yaim , shiss-yeiG , shiss-yqia

Title : Structural basis of heroin and cocaine metabolism by a promiscuous human drug-processing enzyme - Bencharit_2003_Nat.Struct.Biol_10_349
Author(s) : Bencharit S , Morton CL , Xue Y , Potter PM , Redinbo MR
Ref : Nat Struct Biol , 10 :349 , 2003
Abstract : We present the first crystal structures of a human protein bound to analogs of cocaine and heroin. Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that catalyzes the hydrolysis of heroin and cocaine, and the detoxification of organophosphate chemical weapons, such as sarin, soman and tabun. Crystal structures of the hCE1 glycoprotein in complex with the cocaine analog homatropine and the heroin analog naloxone provide explicit details about narcotic metabolism in humans. The hCE1 active site contains both specific and promiscuous compartments, which enable the enzyme to act on structurally distinct chemicals. A selective surface ligand-binding site regulates the trimer-hexamer equilibrium of hCE1 and allows each hCE1 monomer to bind two narcotic molecules simultaneously. The bioscavenger properties of hCE1 can likely be used to treat both narcotic overdose and chemical weapon exposure.
ESTHER : Bencharit_2003_Nat.Struct.Biol_10_349
PubMedSearch : Bencharit_2003_Nat.Struct.Biol_10_349
PubMedID: 12679808
Gene_locus related to this paper: human-CES1

Title : A complete sequence of the T. tengcongensis genome - Bao_2002_Genome.Res_12_689
Author(s) : Bao Q , Tian Y , Li W , Xu Z , Xuan Z , Hu S , Dong W , Yang J , Chen Y , Xue Y , Xu Y , Lai X , Huang L , Dong X , Ma Y , Ling L , Tan H , Chen R , Wang J , Yu J , Yang H
Ref : Genome Res , 12 :689 , 2002
Abstract : Thermoanaerobacter tengcongensis is a rod-shaped, gram-negative, anaerobic eubacterium that was isolated from a freshwater hot spring in Tengchong, China. Using a whole-genome-shotgun method, we sequenced its 2,689,445-bp genome from an isolate, MB4(T) (Genbank accession no. AE008691). The genome encodes 2588 predicted coding sequences (CDS). Among them, 1764 (68.2%) are classified according to homology to other documented proteins, and the rest, 824 CDS (31.8%), are functionally unknown. One of the interesting features of the T. tengcongensis genome is that 86.7% of its genes are encoded on the leading strand of DNA replication. Based on protein sequence similarity, the T. tengcongensis genome is most similar to that of Bacillus halodurans, a mesophilic eubacterium, among all fully sequenced prokaryotic genomes up to date. Computational analysis on genes involved in basic metabolic pathways supports the experimental discovery that T. tengcongensis metabolizes sugars as principal energy and carbon source and utilizes thiosulfate and element sulfur, but not sulfate, as electron acceptors. T. tengcongensis, as a gram-negative rod by empirical definitions (such as staining), shares many genes that are characteristics of gram-positive bacteria whereas it is missing molecular components unique to gram-negative bacteria. A strong correlation between the G + C content of tDNA and rDNA genes and the optimal growth temperature is found among the sequenced thermophiles. It is concluded that thermophiles are a biologically and phylogenetically divergent group of prokaryotes that have converged to sustain extreme environmental conditions over evolutionary timescale.
ESTHER : Bao_2002_Genome.Res_12_689
PubMedSearch : Bao_2002_Genome.Res_12_689
PubMedID: 11997336
Gene_locus related to this paper: thete-DAP2 , thete-LIPA , thete-LIPA3 , thete-MHPC , thete-MHPC2 , thete-MHPC3 , thete-MHPC4 , thete-PLDB , thete-TTE1809 , thetn-DAP2.2

Title : Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 - Jin_2002_Nucleic.Acids.Res_30_4432
Author(s) : Jin Q , Yuan Z , Xu J , Wang Y , Shen Y , Lu W , Wang J , Liu H , Yang J , Yang F , Zhang X , Zhang J , Yang G , Wu H , Qu D , Dong J , Sun L , Xue Y , Zhao A , Gao Y , Zhu J , Kan B , Ding K , Chen S , Cheng H , Yao Z , He B , Chen R , Ma D , Qiang B , Wen Y , Hou Y , Yu J
Ref : Nucleic Acids Research , 30 :4432 , 2002
Abstract : We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
ESTHER : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedSearch : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedID: 12384590
Gene_locus related to this paper: ecoli-Aes , ecoli-yafa , ecoli-ycfp , ecoli-yqia , ecoli-YfhR , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : Biosynthesis and combinatorial biosynthesis of pikromycin-related macrolides in Streptomyces venezuelae - Xue_2001_Metab.Eng_3_15
Author(s) : Xue Y , Sherman DH
Ref : Metab Eng , 3 :15 , 2001
Abstract : Pikromycin-related macrolides have recently attracted significant research interest because they are structurally related to the semisynthetic ketolide antibiotics that have demonstrated promising potential in combating multi-drug-resistant respiratory pathogens. Cloning and in-depth studies of the pikromycin biosynthetic gene cluster from Streptomyces venezuelae have led to new avenues in modular polyketide synthases, deoxysugar biosynthesis, cytochrome P450 hydroxylase, secondary metabolite gene regulation, and antibiotic resistance. Moreover, the knowledge and tools used for these studies are proving to be valuable in the development of advanced technologies for combinatorial biosynthesis of new macrolide antibiotics. This review summarizes these new developments and introduces S. venezuelae as a powerful new system for secondary metabolite pathway engineering from bench-top genetic manipulation to product fermentation.
ESTHER : Xue_2001_Metab.Eng_3_15
PubMedSearch : Xue_2001_Metab.Eng_3_15
PubMedID: 11162229

Title : Genetic architecture of the polyketide synthases for methymycin and pikromycin series macrolides - Xue_2000_Gene_245_203
Author(s) : Xue Y , Wilson D , Sherman DH
Ref : Gene , 245 :203 , 2000
Abstract : The methymycin and pikromycin series of antibiotics are structurally related macrolides produced by several Streptomyces species, including Streptomyces venezuelae ATCC 15439, which produces both 12-membered ring macrolides methymycin, neomethymycin, and 14-membered ring macrolides pikromycin and narbomycin. Cloning and sequencing of the biosynthetic gene clusters for these macrolides from three selected Streptomyces strains revealed a common genetic architecture of their polyketide synthases (PKSs). Unlike PKS clusters of other 14-membered ring macrolides such as erythromycin and oleandomycin, each of the pikromycin series producers harbors a six module PKS cluster, in which modules 5 and 6 are encoded on two separate proteins instead of one bimodular protein, as well as a thioesterase II gene immediately downstream of the main PKS gene. The results shed new light on the evolution of modular PKSs and provide further evidence on the regulation of methymycin and pikromycin production in S. venezuelae ATCC 15439.
ESTHER : Xue_2000_Gene_245_203
PubMedSearch : Xue_2000_Gene_245_203
PubMedID: 10713461
Gene_locus related to this paper: strve-PIKAV

Title : A gene cluster for macrolide antibiotic biosynthesis in streptomyces venezuelae: architecture of metabolic diversity. -
Author(s) : Xue Y , Zhao L , Liu Hw , Sherman DH
Ref : Proceedings of the National Academy of Sciences of the United States of America , 95 :12111 , 1998
PubMedID: 9770448
Gene_locus related to this paper: strve-PIKAIV , strve-PIKAV