ACS Sustainable Chemistry & Engineering
·
2022
·
IF 9.224
Zixin Zhong,Haolan Liu,Ruru Zhou,Boyong Ye,Jie Fu,Zhaoyin Hou
3-Hydroxybutyric acid (3-HBA) is an important monomer for manufacturing biodegradable polymers such as polyhydroxyalkanoates, which are currently produced via an expensive and time-consuming microbial fermentation route. Herein, the catalytic synthesis of 3-HBA via the selective oxidation of 1,3-butanediol (1,3-BDO) in the presence of molecular oxygen is reported for the first time. It was found that the PtSb2 alloy could catalyze the selective formation of 3-HBA, and the selectivity of 3-HBA was 82.3% at a 1,3-BDO conversion level of 95.5%. The calculated turnover frequency of each surface Pt atom in the PtSb2/AC catalyst was 344.3 h–1 at 70 °C. The characterization results indicated that the prominent performance of the PtSb2 alloy over monometallic Pt nanoparticles could be because the alloy could promote the tandem oxidation of the 3-hydroxybutyraldehyde (3-HBAD) intermediate to 3-HBA and reduce the dehydration of 3-HBAD to the byproduct. At the same time, the PtSb2 alloy was also effective for the selective oxidation of several diols to hydroxyl-substituted acids.
研究领域:
化学工程
·
催化科学
·
材料科学
✓ 已验证
DOI
高影响因子
ORGANIC PROCESS RESEARCH & DEVELOPMENT
·
2020
·
IF 3.023
Zeyu Yang,Wenjie Ye,Youyu Xie,Qinghai Liu,Rong Chen,Hualei Wang,Dongzhi Wei
Bioreductions catalyzed by alcohol dehydrogenases (ADHs) play an important role in the synthesis of chiral alcohols. However, the synthesis of ethyl (S)-4-chloro-3-hydroxybutyrate [(S)-CHBE], an important drug intermediate, has significant challenges concerning high substrate or product inhibition toward ADHs, which complicates its production. Herein, we evaluated a novel ADH, SmADH31, obtained from the Stenotrophomonas maltophilia genome, which can tolerate extremely high concentrations (6 M) of both substrate and product. The coexpression of SmADH31 and glucose dehydrogenase from Bacillus subtilis in Escherichia coli meant that as much as 660 g L–1 (4.0 M) ethyl 4-chloroacetoacetate was completely converted into (S)-CHBE in a monophasic aqueous system with a >99.9% ee value and a high space-time yield (2664 g L–1 d–1). Molecular dynamics simulation shed light on the high activity and stereoselectivity of SmADH31. Moreover, five other optically pure chiral alcohols were synthesized at high concentrations (100–462 g L–1) as a result of the broad substrate spectrum of SmADH31. All these compounds act as important drug intermediates, demonstrating the industrial potential of SmADH31-mediated bioreductions.
研究领域:
生物化学
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药物化学
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酶工程
✓ 已验证
DOI
高影响因子
TRENDS IN BIOTECHNOLOGY
·
2024
·
IF 14.3
Jian Li,Xu Zhang,Zi-Xin Peng,Jian-Hai Chen,Jian-Hui Liang,Li-Qing Ke,Dan Huang,Wen-Xiang Cheng,Sien Lin,Gang Li,Rui Hou,Wen-Zhao Zhong,Zheng-Jie Lin,Ling Qin,Guo-Qiang Chen,Peng Zhang
The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate- co -4-hydroxybutyrate) [P(3HB- co -4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB- co -4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB- co -4HB) scaffold for bone regeneration.
研究领域:
组织工程
·
再生医学
·
细胞代谢
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Rong Ma,Yuge Zhou,Weifan Huang,Xiaoni Kong
Ethnopharmacological relevance Epimedium Tourn. ex L. is a traditional Chinese medicine used for thousands of years in China to treat forgetfulness. Icariin is a principal component of the genus Epimedium . Aim of the study The metabolic mechanism of icariin treating forgetfulness is explored. Materials and methods A D-galactose-induced senescent mouse model was employed. The cognitive performance of mice was assessed in the fear conditioning test. Hippocampal pathology was assessed in the immunohistochemistry assay. Plasma metabolome was analyzed using GC-MS method, and the differential metabolites were further identified by UPLC-MS/MS or GC-MS method. The liver function, including ALT and AST, was assessed by enzyme reaction. Icariin was administered intraperitoneally at 50 and 100 mg/kg. Mice were administered five consecutive days per week for 8 weeks. Results Icariin treatment improved hippocampus-related fear memory but not amygdala-related memory, whereas Pexidartinib (PLX3397), a microglial scavenger, did not. Icariin treatment maintained the TMEM119-positive microglial population and decreased the accumulation of the senescent biomarker p16 in the dorsal hippocampus in senescent mouse brains, whereas PLX3397 did not. Notably, p16 in the CA2 subregion significantly decreased in icariin-treated mice than the other hippocampal subregions. The senescent mice exhibited the circulating metabolic characteristics of mild ketoacidosis, active tricarboxylic acid (TCA) cycle, lactic acidosis, hyperglycemia, active detoxification, active cis-oleic acid metabolism, and inhibitory GABA shut. R-3-hydroxybutyric acid primarily produced in the liver was selectively and robustly decreased by icariin treatment, which was not observed with PLX3397. The TCA cycle was rescued in senescent mice by icariin treatment. Icariin also protected liver function (plasma ALT) in D-gal-induced senescent mice. Conclusions Icariin may protect mouse hippocampal cognition from D-gal-induced senescence by protecting microglial homeostasis, and facilitating the utilization of R-3-hydroxybutyric acid is one of the underpins.
研究领域:
神经科学
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药理学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2015
·
IF 2.871
Yu-Cai He,Zhi-Cheng Tao,Yun Ding,Dan-Ping Zhang,Yin-Qin Wu,Yun Lu,Feng Liu,Yu-Feng Xue,Cheng Wang,Jian-He Xu
To avoid adding NAD + and effectively transform ethyl 4-chloro-3-oxobutanoate, the mixture of l -glutamine (200 mM) and d -xylose (250 mM) was added into in n -butyl acetate–water (10:90, v/v) biphasic system instead of NAD + for increasing the biocatalytic efficiency. To further improve the synthesis of optically pure ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ), β-cyclodextrin was also added into this reaction media, and ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ) could be effectively synthesized from 800 mM ethyl 4-chloro-3-oxobutanoate in the yield of 100% by whole-cells of recombinant E. coli CCZU-A13. Finally, the possible mechanism for improving the reductase activity by supplementation of l -glutamine, d -xylose and β-CD was proposed. In conclusion, this strategy has high potential for the effective biosynthesis of ethyl ( R )-4-chloro-3-hydroxybutanoate (>99% ee ).
研究领域:
生物化学
·
酶工程
·
合成生物学
✓ 已验证
DOI
高影响因子
Molecular Catalysis
·
2024
·
IF 3.9
Xuecai Wei,Xiaoyang Yue,Quan Yuan,Ying He,Li Ma,Liya Zhou,Guanhua Liu,Yunting Liu,Yanjun Jiang
Ethyl ( S )-4‑chloro-3-hydroxybutyrate [( S )-CHBE] is attractive as a necessary intermediate for the production of highly valued products in pharmaceutical industries. Nowadays, alcohol dehydrogenases play an increasingly essential role in the asymmetric synthesis of chiral alcohols. In this work, a nicotinamide adenine dinucleotide (NADH)-dependent alcohol dehydrogenase from Pseudomonas bacterium ( Pb ADH) was obtained by genome mining method and identified to exhibit an excellent tolerance against the high substrate and product concentrations. For the regeneration of NADH, Bacillus megaterium glucose dehydrogenase ( Bm GDH) was successfully co-expressed with Pb ADH in E. coli cells. So much as 3.5 M (574 g/L) ethyl 4-chloroacetoacetate (COBE) can be converted to ( S )-CHBE completely with a > 99 % ee value under the catalysis by recombinant cells, even in a monophasic aqueous media with a single batch charge of substrate. In addition, in order to verify the substrate scope of Pb ADH, six other α/β-ketone esters and aromatic ketones were also evaluated as substrates at high substrate concentrations (100–650 g/L), and the corresponding chiral alcohols with highly optical purity were also achieved by co-expressed E. coli cells.
研究领域:
生物化学
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酶工程
·
制药工业
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Communications
·
2021
·
IF 3.383
Bushra Naureen,A.S.M.A. Haseeb,W.J. Basirun,Farina Muhamad
Tissue degeneration due to diseases, accidents, and wars is a worldwide issue. One of the methods used by regenerative medicine (RM) to aid tissue repair is by using a biodegradable tissue engineering scaffold (TES). Different body tissues have variable regeneration abilities, and hence, they require TES with variable degradation rates. This paper focuses on synthesising four polyurethane foam scaffolds (PUFS) with variable degradation rates based on the concentration of incorporated chain extender (CE) poly[(R)-3-hydroxybutyrate] (P3HB). The polyol employed is poly (propylene fumarate) (PPF) along with aliphatic 1,6-hexamethylene diisocyanate (HDI). GPC provided the molecular weight (M n = 455.67 g mol −1 , M w = 587.15 g mol −1 ) and PDI (1.29) of the PPF. FTIR and 1 H and 13 C NMR confirmed the proposed structures (C C, COOR, and NHCOO) of the PUFS. The FESEM images revealed a bimodal pore structure , with random, irregular, interconnected pores (242–340 µm) and discrete void spaces (735–860 µm). The size of PUFS pores and void spaces (PU4 > PU3 > PU2 > PU1) is directly proportional to their respective degradation rates. The TGA/DTA curves show a decrease of an onset thermal decomposition temperature from PU1 to PU4 (267.17 ºC PU1, 267.28 ºC PU2, 256.01 ºC PU3 and 240.72 ºC PU4) due to the respective increase in CE concentration. The results of in-vitro degradation analysis at day 70, revealed significant difference between the weight loss (%) of each group (PU1 = 4.09 ± 0.18%, PU2 = 8.03 ± 0.17%, PU3 = 13.14 ± 0.12% and PU4 = 20.21 ± 0.19%). Thus, PUFS with a higher concentration of P3HB have a faster degradation rate due to the associated P3HB hydrolysable ester/-COOR functional group within the PUFS backbone. The chemical structure , bimodal morphology, and variable degradation rate of these PUFS could be employed for various RM applications.
研究领域:
生物材料学
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再生医学
·
高分子化学
✓ 已验证
DOI
高影响因子
Bioresource Technology Reports
·
2018
·
IF 0
Bing-Qian Wang,Bo Peng,Jian-Fei Sun,Chu Wang,Ke Jiang,Jing-Hao Ma,Peng-Qi Zhang,Yu-Cai He
An effecti v e combination pretreatment of bamboo shoot shell (BSS) using Emulsifier OP-10 (0.5%, w/v) in the acidified media (pH 4.0) by autoclaving (120 °C, 40 min) was conducted. After BSS slurry without detoxification was enzymatically hydrolyzed for 96 h, glucose (25.2 g/L) and xylose (7.5 g/L) were obtained from 50 g/L BSS at high yields. HPLC results showed that no potential inhibitors (furfural and 5-hydroxymethylfurfural) formed. In the hydrolysates , an effective biocatalytic synthesis of ethyl ( S )-4-chloro-3-hydroxybutanoate (100% yield; >99% e.e. ) from 1000 mM ethyl 4-chloro-3-oxobutanoate was developed without the extra addition of cofactors within 24 h. In summary, this combination strategy involving biomass pretreatment, enzymatic saccharification , and bioreduction can be developed for producing chiral alcohols.
研究领域:
生物质预处理
·
酶解糖化
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生物催化
·
手性醇合成
✓ 已验证
DOI
PROCESS BIOCHEMISTRY
·
2020
·
IF 2.952
Yuan Lu,Hongqian Dai,Hanbing Shi,Lan Tang,Xingyuan Sun,Zhimin Ou
Fe 3 O 4 -Arg was selected as the optimal carrier due to its high activity recovery of immobilized cells in the preparation of Fe 3 O 4 -Arg-Cells. The optimal immobilization conditions for the preparation of Fe 3 O 4 -Arg-Cells were 30 °C, 4 h, pH 7, and 3 g dry yeast. The activity recovery of immobilized cells reached 76.8 %. For a batch reduction in a shaker in an alternating magnetic field, Fe 3 O 4 -Arg-Cells were used as a catalyst to gain ethyl ( R )-4-chloro-3-hydroxybutyrate (( R )-CHBE). For further improvement in reduction productivity, a continuous reduction in the magnetic fluidized bed reactor system (MFBRS) was completed. Under their optimal transformation conditions, it took 24 h for Fe 3 O 4 -Arg-Cells to complete the conversion of ethyl 4-chloro-3-oxobutanoate (COBE) (0.8553 mol/L) in the shaker and only 8 h for the batch reduction in an alternating magnetic field. Continuous reduction in MFBRS provided new ideas for the efficient production of ( R )-CHBE; 1.5882 mol/L (10 mL) of COBE can be completely converted in 6 h. The conversion and enantiomeric excess (e.e.) of ( R )-CHBE were 100 % and above 99.9 % respectively, in the three reaction systems mentioned above.
研究领域:
生物化学
·
合成生物学
·
纳米技术
✓ 已验证
DOI
高影响因子
BIORESOURCE TECHNOLOGY
·
2015
·
IF 4.494
Yu-Cai He,Dan-Ping Zhang,Zhi-Cheng Tao,Yun Lu,Yun Ding,Feng Liu,Zheng-Zhong Zhu,Huan Rui,Gao-Wei Zheng,Xian Zhang
To reduce dependence on the expensive cofactor and effectively biotransform ethyl 4-chloro-3-oxobutanoate, l -glutamine and glycine were found to enhance the content of intracellular NADH and the reductase activity. Adding the mixture of 200 mM of l -glutamine and 500 mM of glycine to the reaction media, a 1.67-fold of reductase activity was increased over the control without the addition of the two compounds. Moreover, β-cyclodextrin (0.4 mol β-cyclodextrin/mol ethyl 4-chloro-3-oxobutanoate) was also added into this reaction media, and the biocatalytic activity of the whole-cell biocatalyst of Escherichia coli CCZU-K14 was increased by 1.34-fold than that without β-cyclodextrin. In this β-cyclodextrin–water media containing l -glutamine (200 mM) plus glycine (500 mM), ethyl ( S )-4-chloro-3-hydroxybutanoate (>99% ee ) could be obtained from 3000 mM ethyl 4-chloro-3-oxobutanoate in the yield of 98.0% after 8 h. All the positive features demonstrate the potential applicability of the bioprocess for the large-scale production of ethyl ( S )-4-chloro-3-hydroxybutanoate.
研究领域:
生物化学
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酶工程
·
有机合成
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 8
·e70510
·
IF 4.2
Songlun Jiang,Xu Zhang,Fanfan Chen,Zifan Zhao,Chenglong Zhang,Yuchun Sun
Bone organoids offer potential for bone regeneration and in vitro organ models. Current limitations in bone organoid culture systems include low efficiency in construction and functionality, as well as increased apoptosis in prolonged cultures of larger sizes. The ketone body 3-hydroxybutyrate (3HB), synthesized in the liver, addresses these challenges effectively. Our findings suggest that 3HB increases intracellular calcium ion (Ca 2+ ) levels in human bone marrow-derived mesenchymal stem cells (hBMSCs) by activating the hydroxycarboxylic acid receptor 2 (HCAR2). This activation initiates the cAMP/PKA/CREB pathway, which elevates the expression of anti-apoptotic genes such as myeloid cell leukemia 1 (MCL1) and B cell lymphoma 2-related protein A1 (BCL2A1), thereby reducing apoptosis. Furthermore, this pathway boosts the expression of osteogenic proteins, including Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP2), facilitating osteogenesis in bone organoids. Consequently, 3HB may enhance the construction of bone organoids that are more mature, larger, and have longer viability. Graphical Our study demonstrates that 3-Hydroxybutyrate (3HB) activates the HCAR2 receptor in hBMSCs, leading to an increase in intracellular calcium levels and subsequent activation of the cAMP/PKA/CREB signaling pathway. This pathway upregulates the expression of the anti-apoptotic molecule MCL1 and early osteogenic factors RUNX2 and BMP2. These dual effects of 3HB, promoting osteogenesis and inhibiting apoptosis, provide a promising strategy for constructing more viable and mature bone organoids with higher efficiency.
研究领域:
再生医学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Dexu Liu,Shuangqing Fu,Wenzhi Xu,Xueyu Fan,Shuo Wang,Shengguo Duan,Wei Li,Honglei Zhang
The utilization of environmentally friendly biopolymer poly(3-hydroxybutyrate) (PHB) as a support for metal catalysts is an unexplored area. Herein, exploring a stable and recyclable heterogeneous palladium (Pd) catalyst based on PHB for the Suzuki cross-coupling reaction is an attractive topic. In this study, a novel hydrophobic and hydrophilic core-shell bead supported Pd catalyst was developed by using PHB particle as a hydrophobic rigid framework and hydrophilic chitosan (CS) as the surface of the supporting matrix to fix Pd nanoparticles (NPs). The results of structural characterization showed that the Pd NPs with a small average size of 2.3±0.82 nm were uniformly distributed on the surface of the PHB-CS bead with a Pd content of 0.12 wt%. This demonstrated that the PHB-CS bead created a stable coordinated environment for Pd fixation, preventing Pd leaching. Furthermore, the Pd@PHB-CS catalyst exhibited high catalytic efficiency with 99% conversion in the Suzuki reaction under mild conditions, using a solvent mixture of EtOH and H 2 O (1:1) for 0.5 h. It is worth noting that the catalyst exhibits excellent stability, and reusability. It can be reused five times without a significant reduction in activity while maintaining its structural integrity. The successful construction of Pd@PHB-CS will further expand the application of PHB in the field of metal catalysts and may help establish a green and environmentally friendly multifunctional platform for the development of highly recyclable heterogeneous catalysts containing metal nanoparticles.
研究领域:
材料科学
·
催化
·
绿色化学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）