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Biotechnology for Biofuels · 2018 ·Vol. 11 ·期 1 ·1-12 · IF 5.497

Rich biotin content in lignocellulose biomass plays the key role in determining cellulosic glutamic acid accumulation by Corynebacterium glutamicum

Wen Jingbai,Xiao Yanqiu,Liu Ting,Gao Qiuqiang,Bao Jie

Background Lignocellulose is one of the most promising alternative feedstocks for glutamic acid production as commodity building block chemical, but the efforts by the dominant industrial fermentation strain Corynebacterium glutamicum failed for accumulating glutamic acid using lignocellulose feedstock.Results We identified the existence of surprisingly high biotin concentration in corn stover hydrolysate as the determining factor for the failure of glutamic acid accumulation by Corynebacterium glutamicum. Under excessive biotin content, induction by penicillin resulted in 41.7 ± 0.1 g/L of glutamic acid with the yield of 0.50 g glutamic acid/g glucose. Our further investigation revealed that corn stover contained 353 ± 16 μg of biotin per kg dry solids, approximately one order of magnitude greater than the biotin in corn grain. Most of the biotin remained stable during the biorefining chain and the rich biotin content in corn stover hydrolysate almost completely blocked the glutamic acid accumulation. This rich biotin existence was found to be a common phenomenon in the wide range of lignocellulose biomass and this may be the key reason why the previous studies failed in cellulosic glutamic acid fermentation from lignocellulose biomass. The extended recording of the complete members of all eight vitamin B compounds in lignocellulose biomass further reveals that the major vitamin B members were also under the high concentration levels even after harsh pretreatment.Conclusion sThe high content of biotin in wide range of lignocellulose biomass feedstocks and the corresponding hydrolysates was discovered and it was found to be the key factor in determining the cellulosic glutamic acid accumulation. The highly reserved biotin and the high content of their other vitamin B compounds in biorefining process might act as the potential nutrients to biorefining fermentations. This study creates a new insight that lignocellulose biorefining not only generates inhibitors, but also keeps nutrients for cellulosic fermentations.

CAS / MDL: 1405-69-2 58-85-5
研究领域: 微生物学 · 生物化学 · 工业生物技术
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JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY · 2023 · IF 5

Biotin-modified acid-sensitive micelles for enhancing antitumor effect of paclitaxel

Xinran Wang,Jieyi Pan,Haohui Shi,Na Liang,Shaoping Sun

This study was aimed at fabricating tumor targeting and acid-responsive micelles as carriers for paclitaxel (PTX). An amphipathic polymer TOS-Ace-PEG-Bio was designed and synthesized by conjugating α-tocopherol succinate (TOS) with biotinylated polyethylene glycol (PEG-Bio) via acetal bond. The polymer could self-assemble into nanosized micelles and encapsulate PTX. The PTX-loaded micelles possessed appropriate particle size with the mean value of 129.3 ± 0.9  nm . Strong pH dependent PTX release behavior was verified by in vitro drug release study. At cellular level, the PTX-loaded micelles could be selectively internalized by MCF-7 cells. The in vivo study also confirmed their excellent antitumor activity and reduced side effects. Based on these features, the TOS-Ace-PEG-Bio micelles were considered to be promising carriers for delivery of PTX.

研究领域: 药剂学 · 肿瘤学 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2021 · IF 7.46

Electrochemical detection of telomerase in cancer cells based on the in-situ formation of streptavidin-biotin-DNA-biotin networks for signal amplification

Lin Liu,Daohong Wu,Shuang Zhen,Kaiqing Lu,Xinyao Yi,Zhifang Sun

This work reports on a simple and sensitive electrochemical strategy for the detection of telomerase extracted from HeLa cells. It was based on the signal amplification of in-situ performed streptavidin-biotin-DNA-biotin (SA-biotin-DNA-biotin) networks. Specifically, the DNA primer immobilized on a gold electrode was elongated by telomerase. After the hybridization of biotin-DNA-biotin to the extended primer, the in-situ formation of SA-biotin-DNA-biotin networks was initiated on the electrode surface within 10 min through the SA-biotin interactions. The resulting networks created an insulating layer, thus hampering the electron transfer and causing the significant increase in the electrochemical impedance. Telomerase extracted from 2 HeLa cells can be readily measured. The method showed a linear relationship in the range of 50 ∼ 5000 cells/mL. The signal-amplified strategy can be applied to develop novel sensing platforms for the detection of different biomarkers.

CAS / MDL: 321674-73-1 51805-45-9
研究领域: 生物化学 · 癌症研究 · 电化学 · 分子生物学
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APPLIED ORGANOMETALLIC CHEMISTRY · 2022 ·Vol. 36 ·期 7 ·e6759 · IF 4.072

Synthesis, characterization, and antitumor biological evaluation of novel fluorine-containing platinum (IV) complexes

Lihua Chen,Pan Zhao,Jing Yang,Xiali Liao,Bo Yang,Chuanzhu Gao

A series of antitumor platinum (IV) complexes based on ammonia and fluoropyridine carrier groups with biotin and chloride ions as axial groups have been designed and synthesized in this paper. The structures of platinum (IV) complexes were fully characterized by 1 H NMR, ESI-MS, and IR. Such Pt (IV) complexes have certain tumor targeting properties, and the Pt (II) complexes released in the reducing microenvironment could combine with DNA. Compared with cisplatin, complexes S3 and S4 exhibited similar cytotoxicity against SW480, HCT116, and HepG2 cancer cell lines according to in vitro antitumor activity evaluation. Particularly, Complex S2 showed 1.5–3.0 times higher cytotoxicity than cisplatin and picoplatin against selected cell lines. According to the structure–activity relationship, the introduction of fluorine atoms and axial chloride has an important influence on the strong cytotoxic activity of Pt (IV) complex. In addition, the axial biotin molecule increased the targeting of the complex to tumor cells. Overall, the novel fluorine-containing Pt (IV) complex S2 is an attractive antitumor lead compound with further research value.

研究领域: 药物化学 · 肿瘤学 · 生物无机化学
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Biotin and arginine modified hydroxypropyl-β-cyclodextrin nanoparticles as novel drug delivery systems for paclitaxel

Caixia Yan,Na Liang,Qiang Li,Pengfei Yan,Shaoping Sun

A novel biotin and arginine modified hydroxypropyl-β-cyclodextrin (biotin-Arg(pbf)-HP-β-CD) was successfully synthesized. The hydroxyl groups of HP-β-CD on the primary faces were coupled with carboxyl groups of biotin using arginine as the functional spacer. Using biotin-Arg(pbf)-HP-β-CD as the carrier, paclitaxel (PTX)-loaded nanoparticles were developed by modified emulsion solvent evaporation method. The optimized PTX-loaded biotin-Arg(pbf)-HP-β-CD nanoparticles had a mean diameter of 121.9 nm and zeta potential of -57.7 mV. Transmission electron microscopy (TEM) observation revealed that the nanoparticles were spherical in shape. XRD spectra confirmed the successful encapsulation of PTX. Moreover, in vitro and in vivo evaluations were performed to demonstrate the superior antitumor activity of the PTX-loaded nanoparticles. The cellular uptake study demonstrated the biotin receptor-mediated endocytosis of biotin-Arg(pbf)-HP-β-CD nanoparticles and the increase of cellular uptake by introduction of biotin and arginine. It can be concluded that the biotin-Arg(pbf)-HP-β-CD nanoparticles are efficient tumor-targeting drug delivery systems for PTX.

研究领域: 药剂学 · 肿瘤学
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EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS · 2022 · IF 5.589

A biotin-modified and H2O2-activatable theranostic nanoplatform for enhanced photothermal and chemical combination cancer therapy

Chuanjiang Jian,Ying Wang,Huijun Liu,Zongning Yin

Although synergistic effects of photothermal therapy (PTT) and chemotherapy for cancer have been extensively investigated in previous studies, more potential strategies need to be exploited to alleviate severe adverse effects. In this study, a biotin-modified and activatable nanotheranostic system is developed. This system (BPSP/DOX-CyBA) composed of H 2 O 2 -sensitive thioketal (TK) linker, hydrophilic biotin-decorated polyethylene glycol (PEG) segment, hydrophobic polycaprolactone (PCL) segment, could self-assemble into (99 ± 1.3) nm nanoparticles and co-deliver H 2 O 2 -triggered photosensitizer CyBA and cytotoxic drugs DOX to tumor site. In vitro , DOX and CyBA could release rapidly from nanoparticles, CyBA accumulation in the mitochondria causes mitochondrial damage, leading to mitochondrial dysfunctions,while rising the level of ROS in B16F10 cells, and further to promote the micells to trigger release. CyBA could be activated into CyOH and the photothermal therapy was turn “off” into “on”. In BPSP/DOX-CyBA group, the local temperature within tumor reached 50 °C and cell apoptosis rate reached 68.6% under Laser irradiation (650 nm, 1 W/cm 2 ). Fluorescence microscopy and flow cytometry analysis further demonstrated the better uptake efficiency on B16F10 cells with biotin decoration. In a mice B16F10 tumor model, the group with co-delivery CyBA and DOX had the best tumor retention effect, the maximal local temperature increasement and the minimum tumor growth with negligible side effects, suggesting the potential of BPSP/DOX-CyBA nanopalteform that synergistic photothermal therapy and chemotherapy and mitochondria damage as an effective melanoma treatment strategy.

研究领域: 肿瘤学 · 药剂学 · 生物医学工程
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Specific, sensitive, and reliable sensing of cancer cells based on quantum dot/hydrogel-coated double optical fiber ball

Guosheng Zhang,Anqi Han,Nuo Li,Mingya Yang,Guoqing Yan,Zhigang Cao,Jinhui Shi,Sheng Zhou,Lei Shan,Benli Yu

For clinical applications, a sensor of cancer cells should exhibit high sensitivity, have a small and robust sensing structure, and exhibit good anti-interference. This paper presents a novel biosensor for the recognition and concentration detection of biotin receptor (BR)-overexpressed cancer cells. This biosensor uses a hydrogel composed of biotin-quantum dots (BQDs) grafted onto oxidized sodium alginate with carboxymethyl chitosan (BQDs-g-OSA/CMCS) and a double optical fiber ball (DOFB) sensing structure. The developed BQDs-g-QSA/CMCS hydrogel exhibited specific recognition capabilities for cancer cells and an excellent fluorescence stability. Meanwhile, the proposed DOFB structure was small and presented a strong robustness and integrated fluorescence excitation and reception, which are favorable for in vivo sensing. In addition, in-depth study of the sensing performance of the sensor was conducted by utilizing streptavidin (SV) protein and BR-overexpressed cancer cells (leukemia cells, K562). The experimental results revealed a linear relationship between the photoluminescence intensity of the sensor and concentrations of SV and K562, with minimum detection concentrations of 1.62 nM and 1.0 × 10 3 cells/mL, respectively. In addition, the specificity of the sensor was confirmed through investigation of the its response to another BR-overexpressed cancer cell type (lung cancer cells, A549) and normal cells (human gastric mucosal epithelial, GES-1). The sensor exhibited similar responses to A549 as to K562 cells but not to GES-1 cells, which indicates its specificity toward cancer cells with BR overexpression . In summary, the proposed sensor offers important potential for applications in cancer diagnosis and treatment.

研究领域: 生物医学工程 · 癌症诊断
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DRUG DELIVERY · 2019 · IF 3.829

Novel multifunctional triple folic acid, biotin and CD44 targeting pH-sensitive nano-actiniaes for breast cancer combinational therapy

Mengna Liu,Bingjie Wang,Chunjing Guo,Xiaoya Hou,Ziting Cheng,Daquan Chen

In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.

研究领域: 药剂学 · 肿瘤学 · 生物材料科学
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mBio · 2024 · IF 5.1

Chloroflexus aurantiacus acetyl-CoA carboxylase evolves fused biotin carboxylase and biotin carboxyl carrier protein to complete carboxylation activity

Jiejie Shen,Wenping Wu,Kangle Wang,Jingyi Wu,Bing Liu,Chunyang Li,Zijun Gong,Xin Hong,Han Fang,Xingwei Zhang,Xiaoling Xu

Acetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus, a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation. We reveal that BC1 possesses fused BC and BCCP domains, where BCCP could be biotinylated by E. coli or C. aurantiacus BirA on Lys553 residue. Crystal structures of BC1 and BC2 at 3.2 Å and 3.0 Å resolutions, respectively, further reveal a tetramer of two BC1-BC homodimers, and a BC2 homodimer, all exhibiting similar BC architectures. The two BC1-BC homodimers are connected by an eight-stranded β-barrel of the partially resolved BCCP domain. Disruption of β-barrel results in dissociation of the tetramer into dimers in solution and decreased biotin carboxylase activity. Biotinylation of the BCCP domain further promotes BC1 and CTβ-CTα interactions to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-HP via co-expression with a recombinant malonyl-CoA reductase in E. coli cells. This study revealed a heteromeric ACC that evolves fused BC-BCCP but separate CTα and CTβ to complete ACC activity.

CAS / MDL: 28575-34-0
研究领域: 生物化学 · 分子生物学 · 结构生物学 · 微生物学
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ANALYTICA CHIMICA ACTA · 2023 · IF 6.2

A multiple signal amplification photoelectrochemical biosensor based on biotin-avidin system for kanamycin sensing in fish and milk via synergism of g-C3N4 and Ru@SiO2

Jun Yao

Background The residues of kanamycin can accumulate in the human body for a long time and pose serious health risks, including hearing loss , kidney poisoning, and drug allergic reactions. Therefore, it is crucial to develop a rapid, highly sensitive, and low-cost method for detecting kanamycin residues in foods. However, the current methods have limitations such as low sensitivity, expensive instruments, and multiple steps, which make them impractical for use in resource-limited environments and emergencies. In this study, the creation of a multiple-signal amplification photoelectrochemical biosensor to address these aforementioned issues is discussed. Results Herein, we proposed a multiple signal amplification photoelectrochemical (PEC) biosensor based on carboxylated g-C 3 N 4 and avidin functionalized Ru@SiO 2 for the ultrasensitive detection of kanamycin. The carboxylated g-C 3 N 4 was a highly efficient photoactive substance for amplifying photoelectric signals and a substrate for aptamer immobilization. The DOS and PDOS of g-C 3 N 4 were studied by simulation, and the sensing mechanism of the probe at the molecular level was revealed. Meanwhile, using Ru@SiO 2 as a signal amplifying unit, through the cooperative work between Ru@SiO 2 and g-C 3 N 4 , the photoelectric signal could be double amplified to produce an excellent photocurrent response. Under optimized conditions, the photocurrent response of the PEC biosensor to kanamycin was obtained at concentrations from 0.1 nM to 1000 nM with a lower detection limit of 4.1052 × 10 −11  mol L −1 . This protocol demonstrates high sensitivity, brilliant specific recognition ability, excellent reproducibility, and acceptable stability. Significance The first combination of g-C 3 N 4 and avidin-Ru@SiO 2 as photocurrent materials greatly enhanced the sensitivity of the PEC biosensors. Moreover, the specificity and sensitivity of the PEC biosensor were further improved through the specific interaction between kanamycin and aptamer. The photoelectric conversion mechanism based on g-C 3 N 4 and two pathways for enhancing the photocurrent by Ru(byp) 3 2+ were proposed. Through simulations of the DOS and PDOS of g-C 3 N 4 , the sensing mechanism of the probe at the molecular level was revealed. Under the optimum conditions, the PEC biosensor exhibited a wide linear concentration range and a low detection limit.

研究领域: 食品安全检测 · 分析化学 · 生物医学工程
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JOURNAL OF PHYSICAL CHEMISTRY B · 2021 · IF 2.991

New Insights into the Binding Site and Affinity of the Interaction between Biotin and PAMAMs-NH2 via NMR Studies

Minjun Ma,Xueke Gao,Zhaohui Guo,Yan Qiao

Biotin–dendrimer conjugates (such as biotin-PAMAMs-NH2) are important macromolecules in the field of host–guest chemistry and widely used systems for delivery. The similar chemical structures of the inner and outer layers of PAMAM-NH2 make it difficult to illuminate the interaction and the binding affinity of biotin-PAMAMs-NH2. By utilizing NMR techniques including 1H NMR titration, CSSF-TOCSY, STDD methods, and 2D DOSY analysis, we demonstrate a method to sort out these interactions. The methylene protons of the inner and outer layers of PAMAM-NH2 are successfully identified and accurately positioned so that the carboxylic acid groups of biotins are having ionic interactions with the outermost amine groups of PAMAM-NH2. The inner PAMAM-NH2 is protonated when reaching the isoelectric point of PAMAM-NH2, increasing the hydrodynamic radius. On the basis of the NMR experiments, a model is proposed, where the carboxylic acid groups and heterocyclic skeleton of biotin arched over the outer layers of PAMAM-NH2 like a bridge. Furthermore, using STDD epitope mapping, the binding affinity between biotin and PAMAM-NH2 was quantified. The diffusion behavior of biotin-G5 PAMAM-NH2 complex is more complicated than that of biotin-G3 PAMAM-NH2 complex due to steric hindrance. The results provide a theoretical basis for understanding these complicated drug delivery systems.

研究领域: 化学 · 药物递送系统 · 分子相互作用
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Scientific Reports · 2016 ·Vol. 6 ·期 1 ·1-9 · IF 5.228

A sandwich-type electrochemical immunosensor based on the biotin- streptavidin-biotin structure for detection of human immunoglobulin G

Li Yueyun,Zhang Yihe,Jiang Liping,Chu Paul K.,Dong Yunhui,Wei Qin

A sandwich-type immunosensor is designed and fabricated to detect the human immunoglobulin G (HIgG) using polyaniline and tin dioxide functionalized graphene (GS-SnO 2 -PAN) as the platform and biotin-functionalized amination magnetic nanoparticles composite (B-Fe 3 O 4 @APTES) as the label. GS-SnO 2 -PAN is used as the sensing agent to capture the primary anti-HIgG (Ab 1 ) and SnO 2 reduces the stack of GS. The B-Fe 3 O 4 @APTES with a large surface area and excellent biocompatibility captures second antibody (Ab 2 ) efficiently based on the highly selective recognition of streptavidin to biotinylated antibody. The B-Fe 3 O 4 @APTES has better electro-catalytic activity in the reduction of hydrogen peroxide (H 2 O 2 ) and the “biotin-streptavidin-biotin” (B-SA-B) strategy leads to signal amplification. Under optimal conditions, the immunosensor has a wide sensitivity range from 1 pg/L to 10 ng/L and low detection limit of 0.33 pg/L (S/N = 3) for HIgG. The immunosensor has high sensitivity, fast assay rate, as well as good reproducibility, specificity, and stability especially in the quantitative detection of biomolecules in serum samples.

研究领域: 生物医学工程 · 分析化学 · 免疫学
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