MOLECULES
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2025
·Vol. 30
·期 13
·2701
·
IF 4.6
Jie Zhou,Xinrui Wang,Yangyuxin Liu,Xiaochen Li,Mingze Huang,Helong Bai,Jingang Mo
Obesity is a chronic epidemic caused by abnormal fat metabolism. As a key digestive enzyme, pancreatic lipase (PL) is an important target for regulating fat metabolism. The inhibitory potential of 5,10,15,20-Tetrakis (4-aminophenyl) porphyrin (TAPP), 5,10,15,20-Tetrakis (4-hydroxyphenyl) porphyrin (THPP), meso-Tetra (4-carboxyphenyl) porphine (TCPP), Cu (II) meso-Tetra (4-carboxyphenyl) porphine (Cu-TCPP) on PL was studied by enzymatic kinetics, multi-spectral, and molecular simulation technology. THPP, TCPP, TAPP, and Cu-TCPP all had good PL inhibitory activity (IC50range: 97.49–248.70 μM) and were uncompetitive inhibitors. The order of inhibitory ability was: THPP > TCPP > TAPP > Cu-TCPP. The fluorescence quenching mechanism of THPP to PL was a mixed quenching dominated by static quenching, while TCPP, TAPP, and Cu-TCPP were static quenching. The binding of THPP, TCPP and TAPP to PL was mainly driven by hydrogen bonds and van der Waals forces, while Cu-TCPP was mainly driven by a hydrophobic interaction. Four porphyrin compounds changed the conformation of PL, affected the microenvironment of Tyr and Trp residues, and induced changes in the secondary structure of PL, thereby reducing the stability and catalytic activity of PL. Hydrogen bonds played an important role in the binding stability of THPP, TCPP, TAPP, and PL.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Junzhang Chang,Yuxin Zhang,Ben Xing,Zifan Ye,Jingwen Yang,Hongbin Zhang
The development of a methanol-resistant thermostable lipase is of significant importance in biodiesel synthesis. In this study, a semirational design approach was employed to combine targeted mutagenesis and the introduction of N-glycosylation modifications to enhance the activity and stability of Thermomyces lanuginosus lipase. The activity of mutant A113G was 46% higher than that of the wild type. The double mutant A113G/L74N exhibited 33% residual activity after 24 h of incubation in 50% (v/v) methanol at 50 °C. The favorable temperature stability and methanol tolerance permitted a one-step synthesis of biodiesel; A113G/L74N achieved 91.2% and 80.6% biodiesel yield with soybean oil and waste frying oil, respectively. Molecular dynamics simulations demonstrated that hydrogen bonding between branched glycan and the main chain protein plays a pivotal role in stabilizing the protein structure, with the potential to extend over the surface of the main chain protein. Consequently, this study offers a promising and environmentally friendly strategy for biodiesel production.
研究领域:
生物化学
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酶工程
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可再生能源
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BIOCATALYSIS AND BIOTRANSFORMATION
·
2025
·
IF 1.9
Shenhan Xie,Yanyang Sun,Xu Yan,Yu Han,Chunyu Wang,Fengxi Li,Lei Wang,Zhi Wang
An efficient and environmental method was employed to synthesize multi-substituted 2H-pyran from methyl coumalate and β-keto esters or diketones. Porcine pancreas lipase (PPL) can catalyze this transformation in high yields (74–96%) in aqueous medium (H2O: DMSO = 2:1) under mild conditions (60 °C). The reported strategy exhibits high functional group compatibility and broad substrate scope. In addition, it provides access to a variety of tetra-substituted 2H-pyrans which are considered privileged scaffolds with diverse biological activities.
研究领域:
有机化学
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生物催化
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药物化学
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Catalysts
·
2025
·Vol. 15
·期 5
·482
·
IF 4
Yongqi Zeng,Yong Tang,Minglu Xu,Dantong Wang,Zhi Wang,Yin Gao,Lei Wang
Tetrasubstituted furans and their derivatives represent a versatile class of important heterocyclic frameworks widely distributed in natural products. These scaffolds also demonstrate significant potential in pharmaceutical chemistry, materials science, and organic synthesis methodologies. In this study, we successfully established a synergistic catalytic system utilizing benzoylacetonitriles, aldehydes, and benzoyl chlorides as substrates, facilitated by tributylphosphine and immobilized lipase (Novozym 435), to achieve efficient synthesis of cyano-containing tetrasubstituted furans. Under optimized conditions, we obtained a series of target products exhibiting exceptional substrate tolerance with good to excellent isolated yields ranging from 80% to 94%. Additionally, we proposed a reasonable reaction mechanism and verified it through controlled experiments. This methodology not only expands the synthetic utility of lipase in non-natural transformations but also establishes a paradigm of green chemistry for the construction of tetrasubstituted furans.
研究领域:
有机化学
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生物催化
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药物化学
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-19
·
IF 15.7
Peng Han,Xu Qikui,Zhang Ting,Zhu Jiakai,Pan Jinheng,Guan Xiaoyu,Feng Shan,Wu Jianping,Hu Qi
Lipid droplets (LDs) are the main cellular storage sites for triacylglycerols (TAGs), playing an important role in energy homeostasis and cell signaling. Hydrolysis of the stored TAGs begins with conversion of TAGs into diacylglycerols (DAGs) by adipose triglyceride lipase (ATGL), followed by hydrolysis of DAGs by hormone-sensitive lipase (HSL). Despite the central role of HSL in lipolysis, the molecular determinants for its LD association have remained elusive. Here, we report the cryo-EM structure of human HSL at 3.4 Å. Combining this with hydrogen-deuterium exchange mass spectrometry, biochemical and cellular assays, we identify residues 489-538, referred to as the “H-motif”, and the N-terminal 4-helix bundle of HSL as LD-binding motifs mediating direct interaction of HSL with LDs. LD binding mediated by the LD-binding motifs is independent of HSL phosphorylation catalyzed by the cAMP-dependent kinase PKA. Our findings provide insight into the LD binding mechanism of HSL, advancing our understanding of the regulation of lipolysis.
研究领域:
分子生物学
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细胞生物学
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结构生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Lili Xu,Xinyue Geng,Qi Li,Moju Li,Shu Chen,Xiangnan Liu,Xusheng Dai,Xiuhuan Zhu,Xuekun Wang,Hongbo Suo
The enzyme immobilization technology has become a key tool in the field of enzyme applications; however, improving the activity recovery and stability of the immobilized enzymes is still challenging. Herein, we employed a magnetic carboxymethyl cellulose (MCMC) nanocomposite modified with ionic liquids (ILs) for covalent immobilization of lipase, and used Ca-based metal–organic frameworks (MOFs) as the support skeleton and protective layer for immobilized enzymes. The ILs contained long side chains (eight CH 2 units), which not only enhanced the hydrophobicity of the carrier and its hydrophobic interaction with the enzymes, but also provided a certain buffering effect when the enzyme molecules were subjected to compression. Compared to free lipase, the obtained CaBPDC@PPL–IL–MCMC exhibited higher specific activity and enhanced stability. In addition, the biocatalyst could be easily separated using a magnetic field, which is beneficial for its reusability. After 10 cycles, the residual activity of CaBPDC@PPL–IL–MCMC could reach up to 86.9%. These features highlight the good application prospects of the present immobilization method.
研究领域:
生物化学
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酶工程
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Food Bioscience
·
2024
·
IF 4.8
Hui Chen,Xiting Dong,Yongqiang Zhao,Xuxia Zhou,Mengyuan Zhou,Zhihao Xu,Zhe Xu
In this study, oyster peptide sequences with potential inhibitory activity against pancreatic lipase were screened using molecular docking. Inhibition kinetics, ultraviolet and fluorescence spectroscopy, circular dichroism, and in vitro simulated digestion were employed to investigate the inhibitory mechanism and gastrointestinal stability of the peptides NGDAGMV (P-N) and EAGAGGL (P-E) on pancreatic lipase (PL). The results demonstrated that both P-N and P-E could effectively inhibit PL activity, with IC 50 values of 3.122 and 5.781 mmol/L, respectively. The inhibition type was non-competitive. P-N can alter the covalent structure of PL through charge interactions, hydrogen bonding, C-H bonds, pi -sulfur bonds, and pi -alkyl bonds. Meanwhile, P-E can efficiently quench the intrinsic fluorescence of PL and change its secondary structure primarily through static quenching mediated by salt bridges, hydrogen bonds, C-H bonds, and alkyl bonds. This study provides a theoretical basis for using oyster peptides as natural PL inhibitors.
研究领域:
生物化学
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营养学
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食品科学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 5
·1424
·
IF 3.687
Miaad Adnan,Kai Li,Jianhua Wang,Li Xu,Yunjun Yan
A hierarchical mesoporous zeolitic imidazolate framework (ZIF-8) was processed based on cetyltrimethylammonium bromide (CTAB) as a morphological regulating agent and amino acid (l-histidine) as assisting template agent.Burkholderia cepacialipase (BCL) was successfully immobilized by ZIF-8 as the carrier via an adsorption method (BCL-ZIF-8). The immobilized lipase (BCL) showed utmost activity recovery up to 1279%, a 12-fold boost in its free counterpart. BCL-ZIF-8 was used as a biocatalyst in the transesterification reaction for the production of biodiesel with 93.4% yield. There was no significant lowering of conversion yield relative to original activity for BCL-ZIF-8 when continuously reused for eight cycles. This work provides a new outlook for biotechnological importance by immobilizing lipase on the hybrid catalyst (ZIF-8) and opens the door for its uses in the industrial field.Keywords:adsorption method;biodiesel production;Burkholderia cepacialipase (BCL);hexahedral ZIF-8;hierarchical ZIF-8;surfactant
研究领域:
生物技术
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催化化学
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可再生能源
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
·
IF 8.025
Bozhi Tan,Yao Li,Xu Fei,Jing Tian,Longquan Xu,Yi Wang
Octenyl succinic anhydride (OSA) starch is an important edible additive in the food field, and its synthesis method has attracted much attention. Lipase as a biocatalyst can improve the synthesis efficiency of OSA starch, and significantly inhibit the occurrence of side reactions. However, free lipase has not been widely applied in the synthesis of OSA starch due to the difficulty of separation from starch and poor reusability. In this work, a promising strategy for the synthesis of OSA starch catalyzed by lipase immobilized on polydopamine magnetic hydrogel microspheres (PMHM) is reported. The prepared lipase-polydopamine magnetic hydrogel microspheres (L-PMHM) can be uniformly dispersed in starch slurry, which is conducive to the full contact between lipase and starch. L-PMHM (Km =2.6276 μmol/mL) exhibits better affinity to the substrate than free lipase (Km = 3.4301 μmol/mL). Compared with the OSA starch catalyzed by free lipase (DS = 0.0176), the degree of substitution of OSA starch catalyzed by L-PMHM is up to 0.0277 in a short reaction time. In cyclic catalysis, L-PHMM can remain about 48 % of their original activity after 20 reuses and can be quickly separated from the product. These results suggest that L-PMHM has great potential as a biocatalyst for the efficient synthesis of OSA starch.
研究领域:
食品科学
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生物技术
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化学工程
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CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2018
·Vol. 34
·期 2
·279-284
·
IF 1.248
Xu Chao,Yin Xuhan,Zhang Chuan,Chen Hongyue,Huang He,Hu Yi
Various imidazolium and choline-based functional ionic liquids(ILs) comprising different cations and anions were grafted onto Burkholderiacepacia lipase(BCL) through surface amino acids coupling. The catalytic ac-tivity, thermostability, organic solvent tolerance and adaptability to temperature and pH changes of the modified BCL were then evaluated in olive oil hydrolysis reaction. The results showed that different combinations of cations and anions in ILs had important influence on the catalytic performance of the modified lipases. BCL modified with IL [Choline][H 2 PO 4 ] was the most improved lipase, in which increases by 1.2 folds in relative activity, 2.5 folds in typi-cal proton solvent(10% methanol, volume fraction), and 1.4 folds in thermostability(after incubation at 70 °C for 2 h) were achieved in relative toits native form. BCL modified with [HOOCEPEG 350 IM][BF 4 ] had higher optimal tempe- rature and pH, and better thermosability compared with the native and other modified BCLs. The conformational changes of BCLs were also confirmed by fluorescence spectroscopy and circular dichroism spectroscopy.
研究领域:
酶工程
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生物催化
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离子液体
·
蛋白质修饰
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JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC
·
2013
·
IF 2.823
Huaping Dong,Yimin Li,Guodong Sheng,Liujiang Hu
Three different functionalized bentonites including acid activated bentonite ( B a ), organically modified bentonite with cetyltrimethyl ammonium bromide ( B CTMAB ) and the composite by acid activation and organo-modification ( B a-CTMAB ) were prepared, and used for immobilization of lipase from bovine pancreatic lipase by adsorption. The amount of lipase adsorbed on the functionalized bentonites was in the following sequence: B a > B CTMAB > B a-CTMAB , showing the strongest affinity of B a for lipase among the three supports. However, the immobilized lipase on B a-CTMAB showed the highest activity in the hydrolysis of olive oil by 1.67 times of activity of free lipase due to the hydrophobically interfacial activation and enlarged catalytic interface. While, the activity of immobilized lipase on B a was lower than 20% of free lipase’s activity due to the absence of hydrophobic activation and negative impact of excessive hydrogen ions on the surface. The K m values for the immobilized lipase on B a-CTMAB (0.054 g/mL) and B CTMAB (0.074 g/mL) were both lower than that of free lipase (0.115 g/mL), and the V max values were higher for the immobilized lipases, exhibiting a higher affinity of the immobilized lipase toward olive oil than free lipase. In comparison to free lipase, the better resistance to heating inactivation, storage stability and reusability of the immobilized lipases on B a-CTMAB and B CTMAB were also obtained. The results show that the efficient and stable biocatalysts for industrial application can be prepared by using the low-cost bentonite mineral as the supports.
研究领域:
生物化学
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酶工程
·
材料科学
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JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC
·
2013
·
IF 2.823
Ming-Ming Zheng,Lian Wang,Feng-Hong Huang,Ping-Mei Guo,Fang Wei,Qian-Chun Deng,Chang Zheng,Chu-Yun Wan
This study was focused on the enzymatic esterification of rutin and naringin with different free unsaturated fatty acids to produce the corresponding flavonoid esters catalyzed by Novozym 435 under ultrasound pretreatment. An ultrasonic frequency of 25 kHz, power of 200 W for rutin and 150 W for naringin and time of 1 h was determined to guarantee satisfactory degree of esterification and lipase activity. The influence of substrates concentration and molar ratio was investigated subsequently. The optimum production was achieved in component solvent of acetone and 2-methyl-2-butanol for rutin and pure 2-methyl-2-butanol for naringin at 50 °C with flavonoid concentration of 40 mM and flavonoid to fatty acid molar ratio of 1:4, resulting in a flavonoid esters conversion of above 83.2% in relative short reaction time (48–72 h). In optimum conditions, the overall esterification reaction time using the ultrasonic pretreatment process was 24 h shorter than that of mechanical stirring process without damaging the lipase activity.
研究领域:
生物化学
·
食品科学
·
酶工程
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危险品化学品经营许可证（带存储）