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Article: Characteration of a novel arylesterase from probiotics

Li, Bin-Chun / Guo, Tong-Tong / Ding, Guo-Bin

2021 Volume 11, Issue 12, Page(s) 496

Abstract: We prospected a novel arylesterase LggEst from the probiotics : Supplementary information: The online version contains supplementary material available at 10.1007/s13205-021-03053-7. ...

Abstract	We prospected a novel arylesterase LggEst from the probiotics Supplementary information: The online version contains supplementary material available at 10.1007/s13205-021-03053-7.
Language	English
Publishing date	2021-11-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2600522-0
ISSN	2190-5738 ; 2190-572X
ISSN (online)	2190-5738
ISSN	2190-572X
DOI	10.1007/s13205-021-03053-7
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Article: Cucurbitacin E Triggers Cellular Senescence in Colon Cancer Cells via Regulating the miR-371b-5p/TFAP4 Signaling Pathway

Yang, Peng / Lian, Qing / Fu, Rong / Ding, Guo-bin / Amin, Sajid / Li, Zongwei / Li, Zhuoyu

Journal of agricultural and food chemistry. 2022 Feb. 22, v. 70, no. 9

2022

Abstract: The induction of cellular senescence is considered as a potent strategy to suppress cancer progression. Cucurbitacin E (CE) belongs to the triterpenoids and has received substantial attention for its antineoplastic property. However, the function of CE ... ...

Abstract	The induction of cellular senescence is considered as a potent strategy to suppress cancer progression. Cucurbitacin E (CE) belongs to the triterpenoids and has received substantial attention for its antineoplastic property. However, the function of CE on cellular senescence remained elusive. Herein, we revealed that CE significantly induced cellular senescence in colorectal cancer (CRC) cells. The CE effects on the cellular senescence in CRC cells were confirmed by observing the common features of the senescence, such as the enhanced activity of senescence-associated β-galactosidase, γ-H2AX positive staining, and upregulation of senescence-associated proteins including p53, p27, and p21. Moreover, CE exerted pro-senescent effects in CRC cells via attenuating the transcription factor activating enhancer-binding protein 4 (TFAP4) expression, and the ectopic expression of TFAP4 blocked the CE-induced senescence. Mechanistically, CE treatment caused a robust increase in miR-371b-5p, which markedly repressed TFAP4. In contrast, silencing of miR-371b-5p counteracted the percentages of CE-induced senescent cells from 37.49 ± 2.61 to 7.06 ± 0.91% in HCT-116 cells via derepressing TFAP4 to attenuate the expression of p53, p21, and p16. Altogether, these results demonstrated that dietary CE induces CRC cellular senescence via modulating the miR-371b-5p/TFAP4 axis and presents opportunities for potential therapeutic strategies against CRC.
Keywords	cell senescence ; colorectal neoplasms ; food chemistry ; neoplasm progression ; therapeutics ; transcription factors ; triterpenoids
Language	English
Dates of publication	2022-0222
Size	p. 2936-2947.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.1c07952
Database	NAL-Catalogue (AGRICOLA)

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Article: Characteration of a novel arylesterase from probiotics Lacticaseibacillus rhamnosus GG with the preference for medium- and long-chain p-Nitrophenyl esters

Li, Bin-Chun / Guo, Tong-Tong / Ding, Guo-Bin

3 Biotech. 2021 Dec., v. 11, no. 12

2021

Abstract: We prospected a novel arylesterase LggEst from the probiotics Lacticaseibacillus rhamnosus GG by genome mining strategy, and characterized the enzymatic properties in detail. Biochemical characterization revealed that arylesterase LggEst presented high ... ...

Abstract	We prospected a novel arylesterase LggEst from the probiotics Lacticaseibacillus rhamnosus GG by genome mining strategy, and characterized the enzymatic properties in detail. Biochemical characterization revealed that arylesterase LggEst presented high activity at a wide range of temperatures from 25 to 65 °C with maximum activity at 50 °C. LggEst maintained high activity in the pH range from 5.5 to 7.5 with optimum pH of 6.5. LggEst might efficiently hydrolyze a series of aryl substrates p-nitrophenyl esters with different acyl chain lengths. LggEst displayed the Vₘₐₓ from 2.8 to 77.3 μmol min⁻¹ mg⁻¹ protein and the kcₐₜ from 1.8 to 48.8 s⁻¹ with the highest catalytic activity on pNPC6. The KM of LggEst on different substrates varied significantly from 4.9 μM to 5.6 mM with the highest affinity on pNPC10. LggEst exhibited the preference for medium- and long-chain p-nitrophenyl esters. LggEst showed remarkable thermostability at 45 °C. LggEst could be tolerant of several organic solvents at the concentration of 10% and DMSO and methanol at the concentration of 20%. Catalytic activity of LggEst was improved by 12% in the presence of 20% ethylene glycol. LggEst was resistant to high concentrations of sodium citrate and sodium chloride. Notably, enzymatic activity of LggEst was significantly enhanced in the presence of 0.1% sodium deoxycholate at high temperatures.
Keywords	arylesterase ; catalytic activity ; deoxycholic acid ; enzyme activity ; ethylene glycol ; genome ; methanol ; pH ; probiotics ; sodium chloride ; sodium citrate ; thermal stability
Language	English
Dates of publication	2021-12
Size	p. 496.
Publishing place	Springer International Publishing
Document type	Article
ZDB-ID	2600522-0
ISSN	2190-5738 ; 2190-572X
ISSN (online)	2190-5738
ISSN	2190-572X
DOI	10.1007/s13205-021-03053-7
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Article ; Online: Biosynthesized tumor acidity and MMP dual-responsive plant toxin gelonin for robust cancer therapy.

Ding, Guo-Bin / Cao, Huiyan / Zhu, Chenchen / Chen, Fangyuan / Ye, Jiaqi / Li, Bin-Chun / Yang, Peng / Stauber, Roland H / Qiao, Mingqiang / Li, Zhuoyu

Biomaterials science

2024 Volume 12, Issue 2, Page(s) 346–360

Abstract: Among all kinds of anticancer agents, small molecule drugs produce an unsatisfactory therapeutic effect due to the lack of selectivity, notorious drug resistance and side effects. Therefore, researchers have begun to pay extensive attention to ... ...

Abstract	Among all kinds of anticancer agents, small molecule drugs produce an unsatisfactory therapeutic effect due to the lack of selectivity, notorious drug resistance and side effects. Therefore, researchers have begun to pay extensive attention to macromolecular drugs with high efficacy and specificity. As a plant toxin, gelonin exerts potent antitumor activity
MeSH term(s)	Humans ; Mice ; Animals ; Matrix Metalloproteinase 2 ; Ribosome Inactivating Proteins, Type 1/chemistry ; Ribosome Inactivating Proteins, Type 1/genetics ; Ribosome Inactivating Proteins, Type 1/pharmacology ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; MCF-7 Cells ; Neoplasms/drug therapy
Chemical Substances	GEL protein, Gelonium multiflorum (75037-46-6) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Ribosome Inactivating Proteins, Type 1 ; Antineoplastic Agents
Language	English
Publishing date	2024-01-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2693928-9
ISSN	2047-4849 ; 2047-4830
ISSN (online)	2047-4849
ISSN	2047-4830
DOI	10.1039/d3bm01779f
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Article ; Online: Molecularly engineered tumor acidity-responsive plant toxin gelonin for safe and efficient cancer therapy.

Ding, Guo-Bin / Zhu, Chenchen / Wang, Qian / Cao, Huiyan / Li, Bin-Chun / Yang, Peng / Stauber, Roland H / Nie, Guangjun / Li, Zhuoyu

Bioactive materials

2022 Volume 18, Page(s) 42–55

Abstract: Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant- ... ...

Abstract	Due to the unsatisfactory therapeutic efficacy and inexorable side effects of small molecule antineoplastic agents, extensive efforts have been devoted to the development of more potent macromolecular agents with high specificity. Gelonin is a plant-derived protein toxin that exhibits robust antitumor effect via inactivating ribosomes and inhibiting protein synthesis. Nonetheless, its poor internalization ability to tumor cells has compromised the therapeutic promise of gelonin. In this study, a tumor acidity-responsive intracellular protein delivery system ─ functional gelonin (Trx-pHLIP-Gelonin, TpG) composed of a thioredoxin (Trx) tag, a pH low insertion peptide (pHLIP) and gelonin, was designed and obtained by genetic recombination technique for the first time. TpG could effectively enter into tumor cells under weakly acidic conditions and markedly suppress tumor cell proliferation via triggering cell apoptosis and inhibiting protein synthesis. Most importantly, treatment by intravenous injection into subcutaneous SKOV3 solid tumors in a mouse model showed that TpG was much more effective than gelonin in curtailing tumor growth rates with negligible toxicity. Collectively, our present work suggests that the tumor acidity-targeted delivery manner endowed by pHLIP offers a new avenue for efficient delivery of other bioactive substances to acidic diseased tissues.
Language	English
Publishing date	2022-02-11
Publishing country	China
Document type	Journal Article
ISSN	2452-199X
ISSN (online)	2452-199X
DOI	10.1016/j.bioactmat.2022.02.001
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Article ; Online: Cucurbitacin E Triggers Cellular Senescence in Colon Cancer Cells via Regulating the miR-371b-5p/TFAP4 Signaling Pathway.

Yang, Peng / Lian, Qing / Fu, Rong / Ding, Guo-Bin / Amin, Sajid / Li, Zongwei / Li, Zhuoyu

Journal of agricultural and food chemistry

2022 Volume 70, Issue 9, Page(s) 2936–2947

Abstract	The induction of cellular senescence is considered as a potent strategy to suppress cancer progression. Cucurbitacin E (CE) belongs to the triterpenoids and has received substantial attention for its antineoplastic property. However, the function of CE on cellular senescence remained elusive. Herein, we revealed that CE significantly induced cellular senescence in colorectal cancer (CRC) cells. The CE effects on the cellular senescence in CRC cells were confirmed by observing the common features of the senescence, such as the enhanced activity of senescence-associated β-galactosidase, γ-H2AX positive staining, and upregulation of senescence-associated proteins including p53, p27, and p21. Moreover, CE exerted pro-senescent effects in CRC cells via attenuating the transcription factor activating enhancer-binding protein 4 (TFAP4) expression, and the ectopic expression of TFAP4 blocked the CE-induced senescence. Mechanistically, CE treatment caused a robust increase in miR-371b-5p, which markedly repressed TFAP4. In contrast, silencing of miR-371b-5p counteracted the percentages of CE-induced senescent cells from 37.49 ± 2.61 to 7.06 ± 0.91% in HCT-116 cells via derepressing TFAP4 to attenuate the expression of p53, p21, and p16. Altogether, these results demonstrated that dietary CE induces CRC cellular senescence via modulating the miR-371b-5p/TFAP4 axis and presents opportunities for potential therapeutic strategies against CRC.
MeSH term(s)	Cellular Senescence/drug effects ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/genetics ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; DNA-Binding Proteins ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Triterpenes/pharmacology
Chemical Substances	DNA-Binding Proteins ; MicroRNAs ; TFAP4 protein, human ; Transcription Factors ; Triterpenes ; cucurbitacin E (V8A45XYI21)
Language	English
Publishing date	2022-02-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.1c07952
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Article ; Online: Target Discovery of Novel α-L-Rhamnosidases from Human Fecal Metagenome and Application for Biotransformation of Natural Flavonoid Glycosides.

Li, Bin-Chun / Zhang, Tian / Li, Yan-Qin / Ding, Guo-Bin

Applied biochemistry and biotechnology

2019 Volume 189, Issue 4, Page(s) 1245–1261

Abstract: As a green and powerful tool, biocatalysis has emerged as a perfect alternative to traditional chemistry. The bottleneck during process development is discovery of novel enzymes with desired properties and independent intellectual property. Herein, we ... ...

Abstract	As a green and powerful tool, biocatalysis has emerged as a perfect alternative to traditional chemistry. The bottleneck during process development is discovery of novel enzymes with desired properties and independent intellectual property. Herein, we have successfully bioprospected three novel bacterial α-L-rhamnosidases from human fecal metagenome using a combinatorial strategy by high-throughput de novo sequencing combined with in silico searching for catalytic key motifs. All three novel α-L-rhamnosidases shared low sequence identities with reported (< 35%) and putative ones (< 57%) from public database. All three novel α-L-rhamnosidases were over-expressed as soluble form in Escherichia coli with high-level production. Furthermore, all three novel α-L-rhamnosidases hydrolyzed the synthetic substrate p-nitrophenyl α-L-rhamnopyranoside and natural flavonoid glycosides rutin and naringin with some excellent properties, such as high activity in acidic pH, high activity at low or high temperature, and good tolerance for alcohols and DMSO. Our findings would provide a convenient route for target discovery of the promising biocatalysts from the metagenomes for biotransformation and biosynthesis.
MeSH term(s)	Feces/microbiology ; Flavanones/chemistry ; Glycoside Hydrolases/biosynthesis ; Glycoside Hydrolases/chemistry ; Glycoside Hydrolases/genetics ; Glycoside Hydrolases/isolation & purification ; Humans ; Metagenome ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/isolation & purification ; Rutin/chemistry
Chemical Substances	Flavanones ; Recombinant Proteins ; Rutin (5G06TVY3R7) ; Glycoside Hydrolases (EC 3.2.1.-) ; alpha-L-rhamnosidase (EC 3.2.1.40) ; naringenin (HN5425SBF2)
Language	English
Publishing date	2019-06-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	392344-7
ISSN	1559-0291 ; 0273-2289
ISSN (online)	1559-0291
ISSN	0273-2289
DOI	10.1007/s12010-019-03063-5
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Article ; Online: Integration of Polylactide into Polyethylenimine Facilitates the Safe and Effective Intracellular siRNA Delivery.

Ding, Guo-Bin / Meng, Xue / Yang, Peng / Li, Binchun / Stauber, Roland H / Li, Zhuoyu

Polymers

2020 Volume 12, Issue 2

Abstract: Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the ... ...

Abstract	Polyethylenimine (PEI) is a gold standard polymer with excellent transfection efficacy, yet its severe toxicity and nondegradability hinders its therapeutic application as a gene delivery vector. To tackle this problem, herein we incorporated the biodegradable polylactide (PLA) into the branched PEI by synthesizing a PEI-PLA copolymer via a facile synthetic route. PLA modification significantly improved the cytocompatibility of PEI, PEI-PLA copolymer showed much higher cell viability than PEI as verified in three different human cancer cell lines (HCT116, HepG2 and SKOV3). Interestingly, the PEI-PLA copolymer could effectively bind siRNA targeting PKM2, and the obtained polyplex displayed much higher stability in serum than naked siRNA as determined by agarose gel electrophoresis. Moreover, cellular uptake study demonstrated that PEI-PLA could efficiently deliver the Cy5-labled siRNA into the three tested cancer cell lines, and the transfection efficiency is equivalent to the commercial Lipofectamine
Language	English
Publishing date	2020-02-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527146-5
ISSN	2073-4360 ; 2073-4360
ISSN (online)	2073-4360
ISSN	2073-4360
DOI	10.3390/polym12020445
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Article ; Online: Cucurbitacin E Chemosensitizes Colorectal Cancer Cells via Mitigating TFAP4/Wnt/β-Catenin Signaling.

Yang, Peng / Liu, Wen / Fu, Rong / Ding, Guo-Bin / Amin, Sajid / Li, Zhuoyu

Journal of agricultural and food chemistry

2020

Abstract: Chemoresistance and toxicity are the main obstacles that limit the efficacy of 5-fluorouracil (5-FU) in colorectal cancer (CRC) therapy. Hence, it is urgent to identify new adjuvants that can sensitize CRC cells to conventional chemotherapeutic ... ...

Abstract	Chemoresistance and toxicity are the main obstacles that limit the efficacy of 5-fluorouracil (5-FU) in colorectal cancer (CRC) therapy. Hence, it is urgent to identify new adjuvants that can sensitize CRC cells to conventional chemotherapeutic approaches. Cucurbitacin E (CE) is a natural triterpenoid, widely distributed in dietary plants, and shows antitumor effects. Here, we report that CE enhances the sensitivity of CRC cells to chemotherapy via attenuating the expression of adenosine 5'-triphosphate (ATP)-binding cassette transporters ABCC1 and MDR1. Combined with CE-functionalized magnetite nanoparticles and gene ontology analysis, we found that CE-binding proteins may involve Wnt/β-catenin signaling. To validate the findings, β-catenin was upregulated in drug-resistant cell lines, and the synergistic effects of CE and chemotherapeutics were accompanied by the downregulation of β-catenin. Moreover, TFAP4 was identified as an intracellular target of CE. Remarkably, the combination of CE and 5-FU treatment attenuated β-catenin, MDR1, and ABCC1 expressions, while TFAP4 overexpression reversed their expressions by 2.68 ± 0.46-, 0.72 ± 0.44-, and 0.93 ± 0.21-fold, respectively. Thus, our results indicate that CE sensitizes CRC cells to chemotherapy by decreasing the TFAP4/Wnt/β-catenin signaling, suggesting that the dietary compound CE can be used as a chemosensitizing adjuvant for CRC treatment.
Language	English
Publishing date	2020-11-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	241619-0
ISSN	1520-5118 ; 0021-8561
ISSN (online)	1520-5118
ISSN	0021-8561
DOI	10.1021/acs.jafc.0c05551
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Article: Target Discovery of Novel α-L-Rhamnosidases from Human Fecal Metagenome and Application for Biotransformation of Natural Flavonoid Glycosides

Li, Bin-Chun / Zhang, Tian / Li, Yan-Qin / Ding, Guo-Bin

Applied biochemistry and biotechnology. 2019 Dec., v. 189, no. 4

2019

Abstract	As a green and powerful tool, biocatalysis has emerged as a perfect alternative to traditional chemistry. The bottleneck during process development is discovery of novel enzymes with desired properties and independent intellectual property. Herein, we have successfully bioprospected three novel bacterial α-L-rhamnosidases from human fecal metagenome using a combinatorial strategy by high-throughput de novo sequencing combined with in silico searching for catalytic key motifs. All three novel α-L-rhamnosidases shared low sequence identities with reported (< 35%) and putative ones (< 57%) from public database. All three novel α-L-rhamnosidases were over-expressed as soluble form in Escherichia coli with high-level production. Furthermore, all three novel α-L-rhamnosidases hydrolyzed the synthetic substrate p-nitrophenyl α-L-rhamnopyranoside and natural flavonoid glycosides rutin and naringin with some excellent properties, such as high activity in acidic pH, high activity at low or high temperature, and good tolerance for alcohols and DMSO. Our findings would provide a convenient route for target discovery of the promising biocatalysts from the metagenomes for biotransformation and biosynthesis.
Keywords	Escherichia coli ; alcohols ; alpha-L-rhamnosidase ; biocatalysis ; biocatalysts ; biosynthesis ; biotransformation ; databases ; dimethyl sulfoxide ; humans ; hydrolysis ; metagenomics ; naringin ; pH ; rutin ; temperature
Language	English
Dates of publication	2019-12
Size	p. 1245-1261.
Publishing place	Springer US
Document type	Article
ZDB-ID	392344-7
ISSN	0273-2289
ISSN	0273-2289
DOI	10.1007/s12010-019-03063-5
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