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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

The Biosynthesis of D-1,2,4-Butanetriol From d-Arabinose With an Engineered Escherichia coli

Wang Jing,Chen Qiaoyu,Wang Xin,Chen Kequan,Ouyang Pingkai

D-1,2,4-Butanetriol (BT) has attracted much attention for its various applications in energetic materials and the pharmaceutical industry. Here, a synthetic pathway for the biosynthesis of BT from d-arabinose was constructed and optimized in Escherichia coli. First, E. coli Trans1-T1 was selected for the synthesis of BT. Considering the different performance of the enzymes from different organisms when expressed in E. coli, the synthetic pathway was optimized. After screening two d-arabinose dehydrogenases (ARAs), two d-arabinonate dehydratases (ADs), four 2-keto acid decarboxylases (ADXs), and three aldehyde reductases (ALRs), ADG from Burkholderia sp., AraD from Sulfolobus solfataricus, KivD from Lactococcus lactis IFPL730, and AdhP from E. coli were selected for the bio-production of BT. After 48 h of catalysis, 0.88 g/L BT was produced by the recombinant strain BT5. Once the enzymes were selected for the pathway, metabolic engineering strategy was conducted for further improvement. The final strain BT5ΔyiaEΔycdWΔyagE produced 1.13 g/L BT after catalyzing for 48 h. Finally, the fermentation conditions and characteristics of BT5ΔyiaEΔycdWΔyagE were also evaluated, and then 2.24 g/L BT was obtained after 48 h of catalysis under the optimized conditions. Our work was the first report on the biosynthesis of BT from d-arabinose which provided a potential for the large-scale production of d-glucose-based BT.

研究领域: 生物化学 · 微生物学 · 合成生物学
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NEW JOURNAL OF CHEMISTRY · 2021 ·Vol. 46 ·期 2 ·592-598 · IF 3.591

A four-component domino reaction for the synthesis of novel bridgehead nitrogen-containing pyrido[1,2-d][1,4]diazepines

Rui Wang,Wei Zhang,Ying Tang,Ze-Hui Qi,Yuan-Hui Yu,Hong-Bo Tan,Dian-Yong Tang,Zhi-Gang Xu,Zhong-Zhu Chen

An efficient one-pot four-component reaction for the synthesis of a new family of novel bridgehead nitrogen-containing pyrido[1,2-d][1,4]diazepines has been described and its mechanism has been proposed, which follows a ring-closure and ring-cleavage pathway. The protocol involved a cyclization through γ-selective C–C bond formation, an intramolecular Michael addition and a ring-opening of a pyranone ring under refluxing conditions with high to excellent yields. The advantages of this methodology, including the use of easily available raw materials and an inexpensive catalyst, an open-air reaction setup, wide functional group tolerance, and gram-scale synthesis, make the developed methodology a practical way to access novel pyrido[1,2-d][1,4]diazepines and functionalized tricyclic or polycyclic fused 1,4-diazepines as well as novel analogs of important biologically active molecules.

研究领域: 有机化学 · 药物化学 · 生物活性分子合成
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INTERNATIONAL JOURNAL OF FOOD SCIENCE AND TECHNOLOGY · 2018 ·Vol. 53 ·期 8 ·1992-2005 · IF 2.383

Artificial simulated gastrointestinal digestion of four carbohydrates containing beta-d-1 → 4 linkages and new GC-TQ/MS-MS method for characterising released monosaccharides

Huifan Liu,Fan Gong,Fashan Wei,Furao Lai,Xiaoyuan Zhang,Hui Wu

Summary Four types of carbohydrates, including Dendrobium officinale polysaccharide, Dendrobium aphyllum polysaccharide and β-glucans from yeast and barley, were examined, and their structures were found to mainly contain 1,4-linked-β- d -Glc p . Artificially simulated gastrointestinal digestion was conducted to characterise the changes of molecular weight, reducing sugars and released free monosaccharides by high-performance liquid chromatography, kits and the newly developed gas chromatography (GC)-mass spectrometry (MS)/MS analysis, which indicated that high molecular weight and complex spatial structures contributed to delayed monosaccharide release following exposure to digestive solution. The spatial structures of carbohydrates were changed during gastric digestion, but their primary structures were destroyed during intestinal digestion. Additionally, for the developed 7890A/7000 GC-TQ/MS-MS, the new analytical method was successfully used to analyse very low concentrations of monosaccharides in the simulated gastrointestinal digestive system.

CAS / MDL: 9001-75-6
研究领域: 食品科学 · 分析化学 · 营养学
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TETRAHEDRON-ASYMMETRY · 2014 · IF 2.165

Efficient synthesis of an ε-hydroxy ester in a space–time yield of 1580 g L−1 d−1 by a newly identified reductase RhCR

Rui-Jie Chen,Gao-Wei Zheng,Yan Ni,Bu-Bing Zeng,Jian-He Xu

A new NADH-dependent carbonyl reductase Rh CR capable of efficiently reducing the ε-ketoester ethyl 8-chloro-6-oxooctanoate (ECOO) to give ethyl ( S )-8-chloro-6-hydroxyoctanoate [( S )-ECHO], an important chiral precursor for the synthesis of ( R )-α-lipoic acid, was identified from Rhodococcus sp. ECU1014. Using recombinant Escherichia coli cells expressing Rh CR and glucose dehydrogenase used for the regeneration of cofactor, 440   g L −1 (2   M) of ECOO were stoichiometrically converted to ( S )-ECHO in a space–time yield of 1580   g   L −1   d −1 without the external addition of any expensive cofactor.

研究领域: 生物催化 · 酶工程 · 合成化学 · 生物技术
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JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY · 2026 ·Vol. 40 ·期 5 ·e70877 · IF 3.6

Patulin Affects the Hydroxylation of Vitamin D by Downregulating 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1) Expression and Interfering Their Substrate Binding Sites

Shangyun Lu,Jing Gao,Huixia Zhang,Chao Fan,Ziling Liu,Qi An,Mengge Ren,Yuchen Bai,Fubin Qiu

Patulin (PAT) is a mycotoxin that grows on various fruits and grains, and its toxicity research mainly focuses on organ toxicity. However, the research on its impact on nutritional metabolism is still unclear. Vitamin D is an important nutrient and has been reported to have multiple physiological functions. Vitamin D deficiency has been reported to be associated with the risk of developing diseases such as fatal cancers, autoimmune disorders, cardiovascular disease, neurocognitive function impairment, and type 2 diabetes. However, vitamin D need to be converted into biologically active forms through two steps of hydroxylation in the liver or kidney by 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1). In this study, we found that PAT can cause liver and kidney injury, and affect the levels of activated vitamin D products 25(OH)D and 1,25(OH) 2 D. Specifically, we demonstrated that PAT affects the hydroxylation of vitamin D by downregulating 25-hydroxylase (CYP2R1) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1) expression and interfering their substrate binding sites. This study can provide a basis for a more comprehensive assessment of the impact of environmental pollution, food safety, and other issues on human health.

✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH · 2022 ·Vol. 41 ·期 1 ·1-17 · IF 12.658

Nanoengineering a metal–organic framework for osteosarcoma chemo-immunotherapy by modulating indoleamine-2,3-dioxygenase and myeloid-derived suppressor cells

Fan Qingxin,Zuo Jing,Tian Hailong,Huang Canhua,Nice Edouard C.,Shi Zheng,Kong Qingquan

Background The high postoperative recurrence rate and refractoriness of relapsed tumors are still a conundrum for the clinical management of osteosarcoma (OS). New therapeutic options are urgently needed. Depriving the nourishment of myeloid-derived suppressor cells is a novel strategy to improve the immunosuppressive tumor microenvironment for enhanced OS therapy.Methods We synthesized a hyaluronic acid (HA)-modified metal–organic framework for combinational chemotherapy and immunotherapy of OS. Zeolitic Imidazolate Framework-8 (ZIF-8) was prepared by a one-pot synthetic method, Gemcitabine (Gem) and D-1-Methyltryptophan (D-1-MT) were loaded into the ZIF-8 during the synthesis process to make ZIF-8@Gem/D-1-MT nanoparticles (NPs). The end product (HA/ZIF-8@Gem/D-1-MT NPs) was obtained by HA modification on the surface of ZIF-8@Gem/D-1-MT NPs. The obtained HA/ZIF-8@Gem/D-1-MT NPs have excellent potential as a drug delivery vector for chemotherapy and immunotherapy in vitro and vivo.Results The results indicate that HA/ZIF-8@Gem/D-1-MT NPs were readily taken up by OS cells, and that the Gem and D-1-MT were effectively released into the acidic environment. The HA/ZIF-8@Gem/D-1-MT NPs could efficiently decrease OS cell viability (proliferation, apoptosis, cell cycle, migration and invasion). And HA/ZIF-8@Gem/D-1-MT NPs could reactivate antitumor immunity by inhibiting indoleamine 2,3 dioxygenase and myeloid-derived suppressor cells. Furthermore, animal experiments confirmed that HA/ZIF-8@Gem/D-1-MT NPs could induce intratumoral immune responses and inhibit tumor growth. Additionally, HA/ZIF-8@Gem/D-1-MT NPs have a good safety profile.Conclusion sOur findings demonstrate that the combination of Gem with D-1-MT brings new hope for the improved treatment of OS, while the generation of the nanosystem has increased the application potential and flexibility of this strategy.

研究领域: 癌症研究 · 纳米技术 · 药学 · 免疫学 · 生物医学工程
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