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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2022 · IF 5.895

Production of High Levels of 3S,3′S-Astaxanthin in Yarrowia lipolytica via Iterative Metabolic Engineering

Hang-Zhi Zhu,Shan Jiang,Jun-Jie Wu,Xue-Rong Zhou,Peng-Yang Liu,Feng-Hong Huang,Xia Wan

Astaxanthin is a highly value-added keto-carotenoid compound. The astaxanthin 3S,3′S-isomer is more desirable for food additives, cosmetics, and pharmaceuticals due to health concerns about chemically synthesized counterparts with a mixture of three isomers. Biosynthesis of 3S,3′S-astaxanthin suffers from limited content and productivity. We engineered Yarrowia lipolytica to produce high levels of 3S,3′S-astaxanthin. We first assessed various β-carotene ketolases (CrtW) and β-carotene hydroxylases (CrtZ) from two algae and a plant. HpCrtW and HpCrtZ from Haematococcus pluvialis exhibited the strongest activity in converting β-carotene into astaxanthin in Y. lipolytica. We then fine-tuned the HpCrtW and HpCrtZ transcriptional expression by increasing the rounds of gene integration into the genome and applied a modular enzyme assembly of HpCrtW and HpCrtZ simultaneously. Next, we rescued leucine biosynthesis in the engineered Y. lipolytica, leading to a five-fold increase in biomass. The astaxanthin production achieved from these strategies was 3.3 g/L or 41.3 mg/g dry cell weight under fed-batch conditions, which is the highest level reported in microbial chassis to date. This study provides the potential for industrial production of 3S,3′S-astaxanthin, and this strategy empowers us to build a sustainable biorefinery platform for generating other value-added carotenoids in the future.

研究领域: 生物技术 · 代谢工程 · 微生物生物技术
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IRANIAN POLYMER JOURNAL · 2024 · IF 2.4

Preparation and characterization of 3s-PLA/CS/nHA drug-loaded composites by supercritical carbon dioxide technology

Yang Guoqian,Liu Mengmeng,Su Yingfeng,Yu Chi

Amidst the relentless innovation in materials science and bone tissue engineering, the quest for next-generation bone graft materials with bespoke functionalities has emerged as a pivotal research domain. This study produced and characterized a novel bone healing material. First, we explained how three-armed polylactic acid (3s-PLA) was created in supercritical carbon dioxide (ScCO 2 ) and utilized as a matrix material. Following that, we described how the solution blending approach was employed to create three-armed polylactic acid/chitosan/nanohydroxyapatite (3s-PLA/CS/nHA) composites. The composites were then drug-loaded with prednisone acetate as a model drug utilizing the supercritical impregnation technique. Ultimately, the Ritger-Peppas model was substantially followed by the drug release of the drug-loaded composites when the in vitro drug-release kinetics of the drug-loaded materials were investigated. The porous structure of 3s-PLA was demonstrated by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR) hydrogen spectroscopy. Morphologic studies using scanning electron microscopy (SEM) revealed the homogeneous distribution of drug in the matrix of the mixtures as well as the porous structure of 3s-PLA and 3s-PLA/CS/nHA. The hydrophilicity of 3s-PLA/CS/nHA was examined by the use of water contact angle (WCA), revealing that the material in question has a hydrophilic water contact angle of 45.69°. Furthermore, research was conducted using one-way tests and investigations to characterize in vitro drug-release carrier materials under various drug conditions and temperatures. The carrier material consistently released up to 84.8% of prednisone acetate over the course of 72 h, demonstrating good control over prolonged release, according to the results. Graphical abstract

CAS / MDL: 9012-76-4 125-10-0
研究领域: 材料科学 · 骨组织工程 · 药物递送系统 · 超临界流体技术
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JOURNAL OF BIOLOGICAL CHEMISTRY · 2021 ·Vol. 297 ·期 1 · IF 5.157

Discovery of cyclohexadepsipeptides with anti-Zika virus activities and biosynthesis of the nonproteinogenic building block (3S)-methyl-l-proline

Bochuan Yuan,Ziwei Wu,Wei Ji,Dong Liu,Xiang Guo,Donghui Yang,Aili Fan,Hongli Jia,Ming Ma,Wenhan Lin

The fungal cyclohexadepsipeptides destruxins (DTXs), isaridins (ISDs), and isariins (ISRs) are nonribosomal peptides whose structures include a 19-membered ring composed of five amino acid residues and one α- or β-hydroxy acid residue. These cyclohexadepsipeptides contain unusual nonproteinogenic amino acid–building blocks and possess a range of antiviral, antibacterial, and other activities. The biosynthetic gene clusters for ISDs and ISRs have not been identified, and the biosynthesis of the nonproteinogenic (3S)-methyl-l-proline residue, which is found in DTXs, ISDs, and many other natural products, lacks full characterization. In an ongoing effort to identify compounds that can inhibit the Zika virus (ZIKV), we examined the extract of marine-derived fungus Beauveria felina SX-6-22 and discovered 30 DTXs, ISDs, and ISRs (1–30) including seven new compounds (1–7). The anti-ZIKV assays showed that 9–12 and 16–18 possess inhibitory activities against ZIKV RNA replication and NS5 (nonstructural protein 5) production in ZIKV-infected A549 cells. We sequenced the genome of B. felina SX-6-22 and identified three biosynthetic gene clusters detx, isd and isr, which are responsible for the biosynthesis of DTXs, ISDs, and ISRs, respectively. Comparative analyses of the three gene clusters clarified the biosynthetic relationships among these cyclohexadepsipeptides. Finally, we characterized the entire biosynthesis of nonproteinogenic building block (3S)-methyl-l-proline. The Δ1-pyrroline-5-carboxylate reductases (P5CRs), also used in the biosynthesis of l-proline, were demonstrated to catalyze the final reduction step in (3S)-methyl-l-proline formation, suggesting potential cross talk between primary and secondary metabolisms. These results provide opportunities for biosynthetic pathway engineering to generate new anti-ZIKV cyclohexadepsipeptides.

研究领域: 药理学 · 微生物学 · 分子生物学 · 生物化学 · 基因组学
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FOOD CHEMISTRY · 2026 · IF 10.4

Direct chiral-selective detection of (3S,3′S)-astaxanthin using hydrogel-based SERS chips

Liru Liu,Ping Cheng,Yingxiao Xiao,Sijin Chen,Yiping Zhang,Weizhu Chen,Fengfu Fu,Zhenyu Lin,Yongqiang Dong

(3 S ,3′ S )-astaxanthin ((3 S ,3′ S )-AST) with excellent physiological activity demands accurate chiral-selective detection, yet conventional methods have inherent limitations and SERS technology lacks relevant applications here. In this study, a chiral-selective hydrogel-based SERS chip was prepared by immobilizing aggregated silver nanocages (a-AgNCs) in polyvinyl alcohol (PVA) hydrogel for specific and sensitive (3 S ,3′ S )-AST detection. The hydrogel realized selective adsorption of (3 S ,3′ S )-AST, and a-AgNCs provided strong SERS enhancement via electromagnetic-chemical synergistic effect. The sensing system showed excellent stability (intra/inter-chip RSD < 4.22%, signal loss <5% in 6 weeks), a semi-logarithmic linear response for (3 S ,3′ S )-AST in 0.5–500 ng/g. Practical detection in Haematococcus pluvialis (HP) and Phaffia rhodozyma yeast (PRY) powders confirmed no (3 S ,3′ S )-AST in PRY, and the detected contents in HP samples were consistent with HPLC results. This chip establishes a rapid and reliable chiral-selective detection method for (3 S ,3′ S )-AST, and expands SERS application in chiral analysis of food-related natural products. Hydrogel SERS chips enable direct chiral-selective detection of (3 S ,3′ S )-astaxanthin with high sensitivity and reliable real-sample applicability. Download: Download high-res image (202KB) Download: Download full-size image

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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 3 ·1-10 · IF 5.3

Enantiomeric analysis of chiral phenyl aromatic compounds by coated capillary electrochromatography based on a MOF-on-MOF stationary phase

Miao Pandeng,Chen Jiaquan,Xu Guangfu,Yu Tao,Du Yingxiang

Chiral phenyl aromatic compounds (CPACs) are widely used in drug development, food/cosmetic production, and other organic synthesis processes, and their different enantiomers have distinct physiological activities and application differences. A double-layer metal–organic framework composite (MOF-on-MOF) was obtained by in situ synthesis of chiral metal–organic framework (CMOM-3S) on the surface of an iron-based metal–organic framework (NH 2 -MIL-101(Fe)). According to our investigation, MOF-on-MOF composite was for the first time applied to the stationary phase of capillary electrochromatography (CEC), and enantioseparations of eight CPACs were accomplished. Compared with single CMOM-3S, the enantioseparation performance of the coated capillary columns based on NH 2 -MIL-101(Fe)@CMOM-3S was improved by 34.07 ~ 720.0%. The R-/S-mandelic acid in actual sample (apricot leaves) was detected by the newly CEC system to be 0.0118 mg mL −1 and 0.0523 mg mL −1 , respectively. The spike recoveries were 96.60 ~ 104.7%, indicating its good stability and accuracy. In addition, the selective adsorption capacity of MOF-on-MOF composites was verified by adsorption experiments. Graphical Abstract

研究领域: 分析化学 · 材料科学
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2026 ·Vol. 60 ·期 31 ·21740-21752 · IF 12.2

Interfacial Electron Transfer Powers Synergistic Fenton-like Oxidation and Enhanced Microbial Metabolism for E2–3S Estrogenic Risk Mitigation

Zhang Wei,Yu Qingmiao,Xue Hongpu,Bao Yi,He Yujie,Geng Jinju

Conjugated estrogens like 17β-estradiol-3-sulfate (E2–3S) are ubiquitous in wastewater and pose latent ecological risks due to their potential conversion into endocrine disruptors. To address the limited removal efficiency of biological treatment and the energy dependence of advanced oxidation processes, we developed a novel biomaterial-coupled system ( P .CE2S–Fe–Zn@NC) to mitigate the estrogenic risks of E2–3S by integrating microbial metabolism with advanced oxidation via interfacial electron transfer. The system achieved a 92.4% reduction in estrogenic activity, significantly outperforming standalone biological (80.2%) and catalytic treatments (38.6%). Mechanistic investigations revealed that the Fe–Zn@NC catalyst established a surface microelectric field that facilitated interfacial electron transfer from bacteria to the catalyst. This electron flux drove a self-sustained Fenton-like reaction, effectively activating bacteria-secreted H 2 O 2 into • OH for oxidative transformation. Concurrently, gene transcriptional changes occurred in the functional bacteria within the coupled system, where the upregulation of respiratory energy metabolism and extracellular electron-transfer genes sustained energy-intensive catabolic processes, specifically desulfation and steroid ring cleavage of E2–3S, as evidenced by upregulated steroid catabolic genes. By synergistically coupling material-driven oxidation with microbe-mediated metabolism, this system reduced the estrogenic activity of the effluent. This study provides a transformative paradigm for bridging microbial bioenergetics with material catalysis, offering a sustainable strategy for remediating latent estrogenic contaminants.

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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2014 · IF 2.045

Solubility Determination and Correlation of (2R,3S,4S,5S)-6-(Hydroxymethyl)-tetrahydro-2H-pyran-2,3,4, 5-tetraol in Fatty Alcohol

Yongzhao Zhang,Xia Guo,Jianbing Ji

(2R,3S,4S,5S)-6-(Hydroxymethyl)-tetrahydro-2H-pyran-2,3,4,5-tetraol (d-glucose) solubility in 1-dodecanol, 1-decanol, and 1-octanol from 343.15 K to 393.15 K was determined, respectively. The solubility of d-glucose increased with an increase in temperature and decreased with the increase of fatty alcohol chain length. The modified UNIQUAC model, S-UNIFAC model, and mS-UNIFAC model were applied to predict the solubility data; the interaction parameters were determined. Of the three models, the modified UNIQUAC model showed better prediction accuracy.

研究领域: 化学工程 · 生物化学
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Polymer Chemistry · 2024 ·Vol. 15 ·期 25 ·2590-2597 · IF 4.1

Novel semi-aromatic polyesters based on the biobased diol 2,2′-((3S,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(ethan-1-ol): synthesis, characterization and properties

Huixuan Xu,Weigang Sun,Zhonglin Wei,Jungang Cao,Dapeng Liang,Yingjie Lin,Haifeng Duan

Herein, we provide details of the synthesis and characterization of a novel 2-carbon-extended diol derived from isomannide, 2,2′-((3S,3aR,6S,6aR)-hexahydrofuro[3,2-b]furan-3,6-diyl)bis(ethan-1-ol) and the corresponding semi-aromatic copolyester (PIeT) based on it and dimethyl terephthalate. This new polyester (PIeT) has a weight-average molecular weight of about 40 000 g mol−1. The NMR analysis showed that the isohexide unit was retained under applied conditions. DSC and WAXD analyses demonstrated that the polyester is semicrystalline.

CAS / MDL: 16853-85-3
研究领域: 材料科学 · 有机化学
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JOURNAL OF MEDICINAL CHEMISTRY · 2021 · IF 7.446

Discovery of N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-1H-pyrazol-5-yl)benzamide (Hu7691), a Potent and Selective Akt Inhibitor That Enables Decrease of Cutaneous Toxicity

Jinxin Che,Xiaoyang Dai,Jian Gao,Haichao Sheng,Wenhu Zhan,Yang Lu,Dan Li,Zizheng Gao,Zegao Jin,Binhui Chen,Peihua Luo,Bo Yang,Yongzhou Hu,Qiaojun He,Qinjie Weng,Xiaowu Dong

Rash is one of the primary dose-limiting toxicities of Akt (protein kinase B) inhibitors in clinical trials. Here, we demonstrate the inhibition of Akt2 isozyme may be a driver for keratinocyte apoptosis, which promotes us to search for new selective Akt inhibitors with an improved cutaneous safety property. According to our previous research, compound 2 is selected for further optimization for overcoming the disadvantages of compound 1, including high Akt2 inhibition and high toxicity against HaCaT keratinocytes. The dihedral angle-based design and molecular dynamics simulation lead to the identification of Hu7691 (B5) that achieves a 24-fold selectivity between Akt1 and Akt2. Hu7691 exhibits low activity in inducing HaCaT apoptosis, promising kinase selectivity, and excellent anticancer cell proliferation potencies. Based on the superior results of safety property, pharmacokinetic profile, and in vivo efficacy, the National Medical Products Administration (NMPA) approved the investigational new drug (IND) application of Hu7691.

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