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International Journal of Clinical and Experimental Pathology · 2015 · IF 1.891

Metabolic changes in rats after intragastric administration of MGCD0103 (Mocetinostat), a HDAC class I inhibitor

Qingwei Zhang,Haiya Wu,Congcong Wen,Fa Sun,Xuezhi Yang,Lufeng Hu

MGCD0103, an isotype-selective HDACi, has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In this study, we developed a serum metabolomic method based on gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of intragastric administration of MGCD0103 on rats. The MGCD0103 group rats were given 20, 40, 80 mg/kg of MGCD0103 by intragastric administration each day for 7 days. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) revealed that intragastric administration of MGCD0103 induced metabolic perturbations. As compared to the control group, the levels of L-alanine, L-isoleucine, and L-leucine of MGCD0103 group decreased. The results indicate that metabolomic methods based on GC-MS may be useful to elucidate side effect of MGCD0103 through the exploration of biomarkers (L-alanine, L-isoleucine, and L-leucine). According to the pathological changes of liver at difference dosage, MGCD0103 is hepatotoxic and its toxity is dose-dependent.

研究领域: 药理学 · 代谢组学 · 毒理学
✓ 已验证 DOI PubMed 高影响因子
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Catalysts · 2022 ·Vol. 12 ·期 9 ·971 · IF 4.501

Characterization of a New Marine Leucine Dehydrogenase from Pseudomonas balearica and Its Application for L-tert-Leucine Production

Zewang Guo,Denghui Chen,Qi Xiong,Miao Liang,Pengfei Li,Zehui Gong,Junzhi Qiu,Liaoyuan Zhang

Leucine dehydrogenase (LeuDH) has emerged as the most promising biocatalyst for L-tert-leucine (L-Tle) production via asymmetric reduction in trimethylpyruvate (TMP). In this study, a new LeuDH namedPbLeuDH from marinePseudomonas balearicawas heterologously over-expressed inEscherichia coli, followed by purification and characterization.PbLeuDH possessed a broad substrate scope, displaying activities toward numerous L-amino acids andα-keto acids. Notably, compared with those reported LeuDHs,PbLeuDH exhibited excellent catalytic efficiency for TMP with aKmvalue of 4.92 mM and akcat/Kmvalue of 24.49 s−1mM−1. Subsequently, L-Tle efficient production was implemented from TMP by whole-cell biocatalysis using recombinantE. colias a catalyst, which co-expressedPbLeuDH and glucose dehydrogenase (GDH). Ultimately, using a fed-batch feeding strategy, 273 mM (35.8 g L−1) L-Tle was achieved with a 96.1% yield and 2.39 g L−1h−1productivity. In summary, our research provides a competitive biocatalyst for L-Tle green biosynthesis and lays a solid foundation for the realization of large-scale L-Tle industrial production.Keywords:leucine dehydrogenase;L-tert-leucine;trimethylpyruvate;reductive amination;whole-cell biocatalysis

研究领域: 生物化学 · 工业微生物学
✓ 已验证 DOI 高影响因子
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CHINESE JOURNAL OF CHEMISTRY · 2015 ·Vol. 33 ·期 12 ·1359-1364 · IF 1.578

Behaviors of Leucine and Isoleucine in Ion Mobility-Quadrupole Time of Flight Mass Spectrometry

Su Guo,Fang Zhang,Haoyang Wang,Manyu Zhang,Zhixu Zhang,Xiang Zhang,Yinlong Guo

In this study, ion mobility separation coupled with tandem mass spectrometry (IM-tandem MS) was utilized to investigate the ionization behaviors of two amino acids including leucine and isoleucine. Under the electrospray ionization (ESI) mode, two protonation sites in each molecular sturcture caused two forms of protomer. One arose from the amino being protonated (amino-protomer) and the other from the carboxyl being protonated (carboxyl-protomer). In the two-dimensional (drift time, m/z ) spectrum, the protomers had the same mass, but the distinguishable drift times and fragmentation patterns. For the characterization purpose, the theoretical collision cross section (CCS) values of the protomers were calculated and proven to be consistent with the experimental. Moreover, the quantified relationship between the amino acids and their protomers was evaluated. It showed that the abundance of the carboxyl-protomer was proportional to the concentration of the amino acid, whereas that of the amino-protomer did not have the same trend. Under the atmospheric pressure chemical ionization (APCI) mode, only the carboxyl-protomer was observed. In addition, the amino-protomer and the cluster ions observed under ESI were absent completely. The results demonstrate that the ionization mode impacts heavily on the ionization behaviors of leucine and isoleucine not only on the form of therir protomers but also on the quantified relationship.

CAS / MDL: 73-32-5 61-90-5
研究领域: 分析化学 · 生物化学
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH · 2024 · IF 3.8

Preparation and Formation Mechanism of Spherical Particles with High Quality: A Case Study of l-Isoleucine

Jingren Li,Ronghua Peng,Wei Li,Shilin Guo,Yanbo Liu,Zhenkai Cen,Dandan Han,Songgu Wu,Junbo Gong

As one of the eight essential amino acids in the human body, l-isoleucine plays an important role in human life metabolism and can be applied as a nutritional supplement and food additive in the food field. However, the crystallization of l-isoleucine is generally flaky with poor powder properties, such as bulk density and flowability, which is not conducive to a wide range of industrial applications. In this study, we successfully prepared large spherical particle crystals via two different ways of crystallization. l-Isoleucine undergoes the evolution from initial round flakes to three-dimensional petal-like structures and finally to spherical particles by evaporation crystallization in the presence of hydroxypropylmethylcellulose (HPMC). l-Isoleucine also aggregates into spherical particles in the acid–base reaction crystallization process by adding a small amount of suitable and volatile bridging liquids, such as cyclohexane and ethyl acetate. In conclusion, both approaches improved the crystal properties of l-isoleucine and produced spherical particles with a larger particle size, higher bulk density, and higher compression resistance, thereby providing new insight into the preparation of high-quality l-isoleucine.

研究领域: 食品科学 · 生物化学 · 材料科学
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Unveiling the Potential of the Alkyl Chain of Isoleucine for Regulating the Electrical Double Layer and Enhancing the Zinc-Ion Battery Performance

Xiang Feng,Mingyan Li,Junyi Yin,Tianyi Cui,Fuxiang Li,Yonghong Cheng,Shujiang Ding,Xin Xu,Jianhua Wang

Amino acids are considered effective additives for regulating the electric double layer (EDL) in zinc-ion battery (ZIB) electrolytes. In comparison to their polar counterparts, nonpolar amino acids have received less attention in research. We demonstrated that isoleucine (ILE), benefiting from its nonpolar alkyl chain, emerges as a highly suitable electrolyte additive for aqueous ZIBs. ILE molecules preferentially adsorb onto the anode surface of zinc metal, subsequently creating a locally hydrophobic EDL facilitated by the alkyl chain. On one hand, this enhances the thermodynamic stability at the anode, while on the other hand, it accelerates the desolvation process of zinc ions, thereby improving the kinetics. Benefiting from the unique properties of ILE molecules, Cu//Zn cells with the ILE additive ultimately achieved an extended cycle life of 2600 cycles with an average coulombic efficiency of 99.695%, significantly outperforming other amino acid additives reported in the literature.

研究领域: 材料科学 · 电化学 · 生物化学
✓ 已验证 DOI 高影响因子
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PHYSICAL CHEMISTRY CHEMICAL PHYSICS · 2016 ·Vol. 18 ·期 15 ·10129-10137 · IF 4.449

A designed lipopeptide with a leucine zipper as an imbedded on/off switch for lipid bilayers

Sijia Wang,Yinxing Shen,Junqi Zhang,Shouhong Xu,Honglai Liu

Thermo-sensitive drug carriers are receiving increasing attention for use with localized hyperthermia at abnormal tissue sites or to easily implement hyperthermia. In this study, a thermo-sensitive lipopeptide was designed, consisting of a carbon chain and a leucine zipper with an amino acid sequence CH3-(CH2)4-CO-NH-VAQLEVK-VAQLESK-VSKLESK-VSSLESK-COOH. They could form dimers by the hydrophobic force at body temperature and separate into single random coils above the melting temperature (Tm). The lipopeptide was mixed with phospholipids to form a hybrid liposome (Lipo-LPe). The Tm of the free lipopeptide and lipopeptide in Lipo-LPe was found to be 48.0 °C and 42.5 °C from circular dichroism data, respectively. Compared with the pure liposome, the phase-transition temperature (Ttr) of Lipo-LPe, which was obtained by differential scanning calorimetry, was increased by about 5 °C, showing an improvement of thermal stability. The drug release rate of Lipo-LPe was slightly decreased at body temperature but greatly increased at mild hyperthermia in vitro. Drug release under intermittent heating was performed, and the reversibility of thermo-sensitive on/off switch was confirmed. Furthermore, Lipo-LPe achieved the maximum amount of cell death under mild hyperthermia. We concluded that Lipo-LPe, as a novel thermo-sensitive drug carrier, provides a promising opportunity for controlling drug release.

CAS / MDL: 25316-40-9
研究领域: 药剂学 · 生物化学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENERGY & FUELS · 2024 · IF 5.2

Kinetic Promotional Effect of Methane Hydrate Formation in the Presence of Leucine

Honggang Yu,Chen Chen,Fei Wang

Recent advancements in energy storage and transportation have identified natural gas hydrates as a viable medium for gas storage and transportation, due to their superior storage capacity and favorable conditions. However, the slow reaction rate of hydrate formation limits its industrial application, necessitating rate enhancement for practical use. In this study, leucine is selected as the promoter for the formation of methane hydrates. The research initially focuses on assessing the promotional effect of varying concentrations of leucine. The findings indicate that higher concentrations of leucine substantially increase the reaction rate and shorten the time required for the process, while maintaining the gas storage capacity. Further investigation using a visual apparatus reveals that elevated reaction rates coincide with higher initial rates of water conversion and an observed discrepancy between gas and liquid consumption. The study concludes by employing bilateral single droplet visualization technology and contact angle characterization to ascertain the critical influence of surface wettability on the rapid formation of hydrates. This holds theoretical significance for applications based on methane hydrates, including the storage and transportation of natural gas.

CAS / MDL: 61-90-5
研究领域: 化学工程 · 能源科学
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AMB Express · 2021 ·Vol. 11 ·期 1 ·1-11 · IF 3.298

Antimicrobial compounds were isolated from the secondary metabolites of Gordonia, a resident of intestinal tract of Periplaneta americana

Ma Yan,Xu Minhua,Liu Hancong,Yu Tiantian,Guo Ping,Liu Wenbin,Jin Xiaobao

Gordonia sp. are members of the actinomycete family, their contribution to the environment improvement and environmental protection by their biological degradation ability, but there are few studies on the antimicrobial activity of their secondary metabolites. Our team isolated and purified an actinomycete WA 4-31 from the intestinal tract of Periplaneta americana, firstly identified the strain WA 4-31 by the morphological characteristics and the phylogenetic analyses, and found it was completely homologous to the strain of Gordonia terrae from the Indian desert. Meanwhile, actinomycin D (1), actinomycin X2 (2), mojavensin A (3) and cyclic (leucine-leucne) dipeptide (4) were obtained from the EtOAc extract from the broth of WA 4-31. Compounds 1–4 showed anti-fungus activities against Candida albicans, Aspergillus niger, A. fumigatus and Trichophyton rubrum, also anti-MRSA and inhibited Escherichia coli in different degree. Interestingly, we found when 3 was mixed with 4 with ratio of 1:1, the activity of the mixture on anti-Candida albicans was better than the single. Besides, compounds 1–3 had varying degrees of antiproliferative activities on CNE-2 and HepG-2 cell lines. These indicated that Gordonia rare actinomycete from the intestinal tract of Periplaneta americana possessed a potential as a source of active secondary metabolites.

研究领域: 微生物学 · 药理学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY · 2025 ·Vol. 41 ·期 4 ·1-15 · IF 4.2

Microbial synthesis of enantiopure (S)-2-methylbutanoic acid via L-isoleucine catabolism in Bacillus spizizenii

Zhao Jing-yi,Gao Fan,Wu Mengru,Li Yang,Chen Yong,Xiao Zijun

Enantiopure ( S )-2-methylbutanoic acid [( S )-2-MBA] is a high-value chiral compound with applications in fragrances, pharmaceuticals, and agrochemicals. However, conventional chemical synthesis lacks stereoselectivity, while existing biosynthetic methods suffer from low yield and purity. Here, we report a novel microbial process using Bacillus spizizenii ATCC 6633 for efficient ( S )-2-MBA production via L-isoleucine catabolism. Through targeted screening of rhizospheric soil isolates and Bacillaceae strains, ATCC 6633 demonstrated superior performance, producing 3.67 g/L ( S )-2-MBA with 99.32% enantiomeric excess ( ee ) under optimized conditions (45 °C, 8% inoculation, 5 g/L glucose, and 8 g/L L-isoleucine). A 58.92% conversion efficiency was achieved, and a simplified purification process recovered 63.90% product with 97.32% purity. Mechanistic studies suggested glucose depletion triggered ( S )-2-MBA accumulation, aligning with starvation-induced secondary metabolism. This cost-effective, eco-friendly approach eliminates racemic separation steps and harsh reagents, positioning ATCC 6633 as a promising biocatalyst for sustainable ( S )-2-MBA production.

研究领域: 生物化学 · 微生物学 · 有机化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Bioengineered · 2020 · IF 2.205

Effect of sodium dodecyl sulfate on the production of L-isoleucine by the fermentation of Corynebacterium glutamicum

Haibo Xiong,Yunpeng Liu,Qingyang Xu

Corynebacterium glutamicum is a safe and popular industrial microorganism that it is gram-positive bacteria with thick cell walls, which hinder the extracellular secretion of products. Surfactant has good surface or interface activity and can destroy the cell membrane of microorganisms. In this study, the surfactant SDS was used to artificially destroy the cell membrane of Corynebacterium glutamicum, increase the permeability of the cell membrane, and increase the ability of the strain to secrete L-isoleucine. This is the first time that surfactants have been applied to the fermentation of Corynebacterium glutamicum. Results indicated that after optimization, the output of L-isoleucine reached 43.67 g/L, which was 13.01% higher than that without sodium dodecyl sulfate. The yield of the by-products, such as valine, leucine, and alanine, was reduced by 72.30%, 64.30%, 71.70%, respectively. This method can promote the production of L-isoleucine while minimizing the damage of SDS to the strain.

研究领域: 生物技术 · 微生物学
✓ 已验证 DOI PubMed 高影响因子
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TRANSGENIC RESEARCH · 2025 ·Vol. 34 ·期 1 ·1-17 · IF 2

Knockout of the Agrobacterium ILVC gene generates a valine-isoleucine auxotrophic strain for plant transformation

Yang Yanhui,Lu Jun,Xue Tianrui,Cao Zhenli,Li Mingjie,Zhang Zhongyi,Wang Rong,Wu Tongyu

The Agrobacterium tumefaciens mediated transformation is the prevailing methodology for plant genetic manipulation; however, A. tumefaciens overgrowth is a common constraint in the process. Exploring auxotrophic A. tumefaciens could reduce overgrowth and enhance plant transformation efficiency. The ILVC gene, which encodes the ketol-acid isomeroreductase, is critical for Valine (Val) and isoleucine (Ile) biosynthesis in some microorganisms. However, its function in A. tumefaciens is unclear. To ascertain the function of ILVC and generate an auxotrophic A. tumefaciens , this study employed an allelic exchange to disrupt the ILVC in A. tumefaciens strain GV3101. This resulted in the loss of ketol-acid isomeroreductase activity and the prevention of Val and Ile biosynthesis, creating a dual-auxotrophic GV3101 ∆ILVC . Transient expression assays in Nicotiana benthamiana transformation demonstrated that the GV3101 ∆ILVC was capable of T-DNA transfer. Moreover, stable genetic transformation analysis in N. benthamiana indicated that the introduction of GV3101 ∆ILVC led to a reduction in overgrowth within infected plant tissues. Additionally, an enhancement in transformation efficiency was observed with the prolongation of the co-cultivation time of the explant-infected strain. This study revealed the function of ILVC and explored a dual-auxotrophic A. tumefaciens for Val and Ile, potentially broadening the utilization of auxotrophic strains in plant genetic transformation.

研究领域: 植物学 · 微生物学 · 遗传学
✓ 已验证 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2021 ·Vol. 22 ·期 22 ·12182 · IF 5.924

Silencing a Simple Extracellular Leucine-Rich Repeat Gene OsI-BAK1 Enhances the Resistance of Rice to Brown Planthopper Nilaparvata lugens

Miaofen Ye,Peng Kuai,Shuting Chen,Na Lin,Meng Ye,Lingfei Hu,Yonggen Lou

Many plant proteins with extracellular leucine-rich repeat (eLRR) domains play an important role in plant immunity. However, the role of one class of eLRR plant proteins—the simple eLRR proteins—in plant defenses against herbivores remains largely unknown. Here, we found that a simple eLRR protein OsI-BAK1 in rice localizes to the plasma membrane. Its expression was induced by mechanical wounding, the infestation of gravid females of brown planthopper (BPH)Nilaparvata lugensor white-backed planthopperSogatella furciferaand treatment with methyl jasmonate or abscisic acid. SilencingOsI-BAK1(ir-ibak1) in rice enhanced the BPH-induced transcript levels of three defense-related WRKY genes (OsWRKY24,OsWRKY53andOsWRKY70) but decreased the induced levels of ethylene. Bioassays revealed that the hatching rate was significantly lower in BPH eggs laid on ir-ibak1plants than wild-type (WT) plants; moreover, gravid BPH females preferred to oviposit on WT plants over ir-ibak1plants. The exogenous application of ethephon on ir-ibak1plants eliminated the BPH oviposition preference between WT and ir-ibak1plants but had no effect on the hatching rate of BPH eggs. These findings suggest that OsI-BAK1 acts as a negative modulator of defense responses in rice to BPH and that BPH might exploit this modulator for its own benefit.Keywords:rice;OsI-BAK1;Nilaparvata lugens;ethylene;plant defense responses;simple extracellular leucine-rich repeat protein

研究领域: 植物学 · 昆虫学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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