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LWT-FOOD SCIENCE AND TECHNOLOGY · 2025 · IF 6.6

Harnessing exogenous AI-2 to improve ethanol tolerance in Lactobacillus plantarum R: Insights from transcriptome and metabolome

Mengchen Li,Bo Li,Binbin Long,Leibin Li,Yang Chen,Mingye Peng,Mengzhou Zhou

Lactobacillus plantarum R is the predominant bacterium widely used in food fermentation. However, it has a low tolerance to ethanol during fermentation, which restricts its broader application in the food industry. Although biofilm formation enhances bacterial resistance to various stresses, regulating biofilm formation in L. plantarum R remains challenging. In this study, we established a pathway for producing autoinducer 2 (AI-2), a quorum-sensing (QS) signaling molecule, by heterologously expressing pfs and LuxS in L. plantarum R. This approach aimed to modulate cell membrane structure and improve bacterial ethanol resistance. The findings showed that exogenous AI-2 significantly enhanced the growth of L. plantarum R under high-ethanol concentration and improved its biofilm formation at different ethanol concentrations. Furthermore, a multi-omics analysis revealed potential mechanisms by which AI-2 improved the tolerance of L. plantarum R to ethanol. Notably, the upregulation of the crr gene, a component of the phosphotransferase system (PTS), enhanced biofilm formation in response to ethanol stress. In addition, differential metabolites enriched in cysteine and methionine metabolic pathways further supported the role of QS in enhancing the tolerance of L. plantarum R to ethanol. These findings lay the groundwork for enhancing the fermentation performance of strains applied in the food fermentation industry, presenting a novel method for expanding the utilization of L. plantarum R in high-ethanol fermentation.

CAS / MDL: 3646-73-9
研究领域: 微生物学 · 食品生物技术 · 分子生物学 · 系统生物学 · 合成生物学 · 发酵技术
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Green Synthesis and Catalysis · 2020 · IF 0

Redesign of a short-chain dehydrogenase/reductase for asymmetric synthesis of ethyl (R)-2-hydroxy-4-phenylbutanoate based on per-residue free energy decomposition and sequence conservatism analysis

Bingmei Su,Lian Xu,Xinqi Xu,Lichao Wang,Aipeng Li,Juan Lin,Lidan Ye,Hongwei Yu

As an important building block for the synthesis of angiotensin-converting enzyme inhibitors, ethyl ( R )-2-hydroxyl-4-phenylbutanoate [( R )-HPBE] has attracted increasing attention. The key to industrial biosynthesis of ( R )-HPBE is a biocatalyst that efficiently reduces ethyl 2-oxo-4-phenylbutanoate (OPBE) with high R -enantioselectivity. This paper proposed a strategy for identifying key residues involved in enantioselectivity control based on per-residue free energy decomposition and sequence conservatism analysis. Using this strategy, 4 nonconservative sites with high energy contribution to binding of OPBE were chosen as engineering targets, generating variant Mu27 with 99% conversion and 98% ( R ) ee value at substrate loading of up to 500 ​mmol/L. MD simulations suggested the higher stability and formation probability of Mu27-OPBE proR prereaction state as key reasons for the excellent R -enantioselectivity of Mu27 towards OPBE. The success in this study provides a viable approach for rational design of alcohol dehydrogenases with high enantioselectivity towards unnatural substrates.

研究领域: 生物化学 · 酶工程 · 计算生物学
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JOURNAL OF PLANT PHYSIOLOGY · 2025 · IF 4.1

Sporopollenin-chitosan microspheres loaded with an endophytic fungus Talaromyces neorugulosus R-209 for promoting development and controlling root rot in pigeon pea

Jin-Xian Fu,Jiao Jiao,Qing-Yan Gai,Yu-Jie Fu,Mo-Nan Wen,Xiao-Qing Wang,Jing He

Plant-beneficial microbes can be effective as biological agents for promoting development and controlling diseases in plants. However, direct inoculation of non-encapsulated plant-beneficial microbes into the soils can affect their vitality and efficacy. A novel bio-based encapsulant, sporopollenin-chitosan microspheres (SCMs), was developed to load an endophytic fungus Talaromyces neorugulosus R-209 with antagonistic activities against the root rot pathogen ( Rhizoctonia solani AG4) and plant growth-promoting functions. The results showed that T. neorugulosus R-209 encapsulated in SCMs ( Tn R-209−SCMs) could significantly enhance fungal spore germination rates and available nitrogen/phosphorus levels in the soil compared to the non-encapsulated fungus. In addition, the preliminary evidence suggests that Tn R-209−SCMs have a basic safety profile for practical applications. Inoculation with Tn R-209−SCMs could effectively promote development and enhance resistance in pigeon pea seedlings by promoting chlorophyll synthesis, improving photosynthesis, and enhancing phenolic compound accumulation. Meanwhile, T. neorugulosus R-209 was found to endogenously colonize root intercellular spaces. Moreover, co-inoculation of Tn R-209−SCMs and R. solani AG4 could reduce host defense responses compared to R. solani AG4-infected roots, as reflected by lower levels of phenolic compound accumulation and pathogenesis-/biosynthesis-related gene expression. Overall, Tn R-209−SCMs is a promising biological agent that can promote development and control root rot in plants, which also provides an innovative approach to biomaterial-supported agricultural practices.

研究领域: 植物科学 · 微生物学 · 农业生物技术 · 生物工程 · 真菌生物学 · 土壤科学 · 植物病理学
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BIORESOURCE TECHNOLOGY · 2016 · IF 4.917

Effective asymmetric bioreduction of ethyl 4-chloro-3-oxobutanoate to ethyl (R)-4-chloro-3-hydroxybutanoate by recombinant E. coli CCZU-A13 in [Bmim]PF6-hydrolyzate media

Yu-Cai He,Zhi-Cheng Tao,Jun-Hua Di,Liang Chen,Lin-Bing Zhang,Dan-Ping Zhang,Gang-Gang Chong,Feng Liu,Yun Ding,Chun-Xia Jiang,Cui-Luan Ma

It was the first report that the concentrated hydrolyzates from the enzymatic hydrolysis of dilute NaOH (3   wt%)-soaking rice straw at 30   °C was used to form [Bmim]PF 6 -hydrolyzate (50:50, v/v) media for bioconverting ethyl 4-chloro-3-oxobutanoate (COBE) into ethyl ( R )-4-chloro-3-hydroxybutanoate [( R )-CHBE] (>99% e.e. ) with recombinant E. coli CCZU-A13. Compared with pure glucose, the hydrolyzates could promote both initial reaction rate and the intracellular NADH content. Furthermore, emulsifier OP-10 (20   mM) was employed to improve the reductase activity. Moreover, Hp-β-cyclodextrin (0.01   mol Hp-β-cyclodextrin/mol COBE) was also added into this bioreaction system for enhancing the biosynthesis of ( R )-CHBE from COBE by E. coli CCZU-A13 whole-cells. The yield of ( R )-CHBE (>99% e.e. ) from 800   mM COBE was obtained at 100% in the [Bmim]PF 6 -hydrolyzate (50:50, v/v) media by supplementation of OP-10 (20   mM) and Hp-β-CD (8   mM). In conclusion, an effective strategy for the biosynthesis of ( R )-CHBE was successfully demonstrated.

研究领域: 生物化学 · 微生物学
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JOURNAL OF BIOMATERIALS APPLICATIONS · 2022 · IF 2.712

The effect of alkyl chain length of (R)-3-Hydroxybutyric alkyl ester on antibacterial activity and its antibacterial mechanism

Zao Cheng,Junfei Gao,Qianqian Liu,Qun Gu

This work describes the relationship between the antibacterial activity and the ester chain length (C1-C8) of (R)-3-Hydroxybutyric ((R)-3-HB) alkyl esters that synthesized from (R)-3-HB acid ((R)-3-HBA) by esterification reaction. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) decrease as the length of the (R)-3-HB alkyl ester chain increases from 1 to 6, but (R)-3-HB-C7 and (R)-3-HB-C8 have their own rules for different microorganisms. Among them, the (R)-3HB-C6 has the relatively best antibacterial and antifungal properties, which MIC were 1.95 mg mL−1 against E. coli and S. aureus; 0.98 mg mL−1 against C. albicans and B. subtilis; 0.49 mg mL−1 against A. niger. Finally, the antimicrobial mechanisms of the (R)-3HB-C6 are revealed, and these include disruption of biofilm and the bacterial wall/membrane, leakage of the intracellular content, and change in the transmembrane potential. These results imply the potential application of (R)-3-HB alkyl ester as new antimicrobial agents; future research can use this as an antibacterial element to synthesize new polymer materials or agents with high-efficiency antibacterial activity.

研究领域: 药物化学 · 微生物学 · 有机化学
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FISH & SHELLFISH IMMUNOLOGY · 2019 · IF 3.298

The hepatoprotective effects of Salvia plebeia R. Br. extract in zebrafish (Danio rerio)

Guanghua Xiong,Yunyun Deng,Zigang Cao,Xinjun Liao,Jun'e Zhang,Huiqiang Lu

Salvia plebeia R. Br. is a traditional Chinese medicinal herb that has been widely used for the treatment of many inflammatory diseases such as hepatitis. However, the underlying molecular mechanism about the hepatoprotective effects of S. plebeia remains largely unknown. Here, we investigated the antioxidant activities and anti-inflammatory effects of ethanol extracts of S. plebeia (SPEE) in the zebrafish model. Firstly, we determined the chemical compositions of SPEE and identified three major constituents by using GC-MS analysis. After that, SPEE exhibited significantly antioxidant properties in the LPS-induced zebrafish embryos, and the enzyme activities of ROS, CAT and SOD were obviously inhibited in a dose-dependent manner. Secondly, SPEE greatly reduced fat vacuoles (HE staining), lipid accumulation (Oil O staining) and hepatocyte fibrosis (Gemori staining) in the thioacetamide (TAA)-induced hepatocyte injury of adult zebrafish. Meanwhile, the NO contents and lipid metabolism-related genes were substantially down-regulated after SPEE exposure. Thirdly, we used RNA-Seq analysis to identify the differentially expressed genes (DEGs) after SPEE exposure in adult zebrafish liver. The results showed that 1289 DEGs including 558 up-regulated and 731 down-regulated were identified between the TAA + SPEE and TAA groups. KEGG pathway and GO functional analysis revealed that steroid biosynthesis , oxidation-reduction and innate immunity were significantly enriched. Mechanistically, SPEE can considerably reduce the cell apoptosis of hepatocytes and promote the translocation of Nrf2 protein from the nucleus to the cytoplasm in TAA-induced zebrafish. Moreover, SPEE can modulate various inflammatory cytokines and immune genes both in the control and H 2 O 2 -stimulated conditions. The pro-inflammatory cytokines such as IL-1β and TNF-α was markedly up-regulated but the anti-inflammatory cytokines such as TGF-β was greatly down-regulated after SPEE treatment. In addition, some key genes in the TLR signaling were also activated in the H 2 O 2 -stimulated conditions. In summary, our results suggested that SPEE had an important role in the antioxidant and anti-inflammatory effects in zebrafish in the near future. Some of the components identified in this study may be served as potential sources of new hepatoprotective compounds for the treatment of inflammatory diseases.

CAS / MDL: 7722-84-1
研究领域: 药理学 · 分子生物学 · 毒理学 · 基因组学
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY · 2022 · IF 7.088

In vitro and in vivo biological evaluation of newly synthesized multi-target 20(R)-panaxadiol derivatives for treating Alzheimer's disease

Lei Pang,Jin Li,Zheng Liu,Yin-Sheng Quan,He Huan Sui,Yi Jia,Fener Chen,Jung Joon Lee,Peng Liu,Zhe-Shan Quan,Qing-Kun Shen,Hong-Yan Guo

An extensive study was performed to discover a series of novel 20( R )-panaxadiol derivatives with various substituents at the 3-OH position as nontoxic, brain-permeable, multi-target leads for treating Alzheimer's disease . In vitro analysis revealed that a compound bearing benzyl-substituted carbamate , which we denoted compound 14a , exhibited the most potent neuroprotective activity, with an EC 50 of 13.17 μM. The neuroprotective effect of compound 14a was slightly more potent than that of donepezil and much more potent than that of 20( R )-panaxadiol. Compound 14a at 7.5–120 μM exhibited low toxicity in various cell lines. In addition, compound 14a exhibited a wide range of biological activities , including inhibiting apoptosis ; inducing tau hyperphosphorylation ; affecting beta-amyloid (Aβ), β-secretase, reactive oxygen species , tumor necrosis factor-α, cyclooxygenase-2, and interleukin-1β production; and promoting Aβ 25-35 disaggregation. The effective permeability of compound 14a across the blood-brain barrier was 26.13 × 10 −6  cm/s, indicating that it can provide adequate exposure in the central nervous system. Further, compound 14a improved learning, memory, and novel object recognition in mice, and in vivo toxicity experiments confirmed a good therapeutic safety range. Thus, compound 14a is a promising multifunctional lead for treating Alzheimer's disease and offers new avenues for natural product-derived anti-Alzheimer's disease drugs.

CAS / MDL: 112-40-3
研究领域: 药理学 · 神经科学 · 药物发现
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS · 2020 · IF 3.209

(S)-1-(5-(4-Methylpiperazin-1-yl)-2,4-dinitrophenyl)pyrrolidine-2-carboxylic acid as a derivatization reagent for ultrasensitive detection of amine enantiomers by HPLC-MS/MS and its application to the chiral metabolite analysis of (R)-1-aminoindan in saliva

Youxi Jin,Yu Pan,Biao Jin,Dongri Jin,Chunbo Zhang

(S)-1-(5-(4-Methylpiperazin-1-yl)-2,4-dinitrophenyl)pyrrolidine-2-carboxylic acid (Pro-PPZ) was employed as a chiral derivatization reagent (CDR) for the efficient enantioseparation and ultrasensitive mass spectrometric detection of chiral amines. Pro-PPZ was prepared from the one-step reaction of 1-(5-fluoro-2,4-dinitrophenyl)-4-methylpiperazine (PPZ) and l -proline. Two amines and two amino acid methyl esters were selected as model chiral amines, which were easily labeled with Pro-PPZ under mild reaction conditions (35 °C for 10 min) generating Pro-PPZ-amine derivatives. The resulting diastereomers were completely separated by reversed-phase liquid chromatography (RP-LC) using an ODS column ( R s = 3.4–17.0 for amines). Ultrasensitive detection limits on femtomolar level were obtained for the tested amines using multiple reaction monitoring (MRM) chromatograms at a single monitoring ion, m/z 289 (0.1–5.0 fmol for amines). The practical metabolite analysis of (R)-1-aminoindan (R-AI) in saliva samples was performed by LC–MS/MS using the Pro-PPZ derivatization method. The method was validated in terms of precision, accuracy, and linearity. Using this method, R-AI concentrations in saliva were determined after a single oral administration of the drug rasagiline to healthy male and female subjects, but no (S)-1-aminoindan (S-AI) was detected, which suggesting that R-AI was not converted into S-enantiomer in the metabolic process. R-AI concentrations in four healthy volunteers ranged from 32.85 nM to 49.45 nM, with an average value of 43.76 nM. To date, there is no LC–MS (or MS/MS) method reported for the enantioselective determination of R-AI in human saliva samples.

研究领域: 分析化学 · 药物代谢 · 临床医学
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Frontiers in Microbiology · 2021 · IF 5.64

Research on the Interaction Mechanism Between α Mino-Phosphonate Derivative Q-R and Harpin-Binding Protein 1 in Tobacco (Nicotiana tabacum) Plants

Huang Maoxi,Yan Yunlong,Wang Li,Chen Jun,Liu Tao,Xie Xin,Li Xiangyang

Amino-phosphonate derivative R-diphenyl-1-(4-methylbenzothiazole-2-amino)-1-(thiphene-2-yl)-methylphosphonate (Q-R) has a high protective anti-tobacco mosaic virus (TMV) activity. However, the mechanism responsible for Q-R’s effect on TMV infection is largely unknown. Here, we studied the expression levels of harpin-binding protein 1 (HrBP1) and pathogenesis-related protein-1a (PR-1a) in TMV-infected tobacco plants by using reverse transcription quantitative real-time PCR. Then, we verified the interactions between Q-R and the HrBP1 protein from Escherichia coli using isothermal titration calorimetry and studied the Q-R-associated assembly of HrBP1 using size-exclusion chromatography. The results showed that the expression levels of HrBP1 and PR-1a genes were significantly increased by Q-R at the transcriptional level in TMV-infected tobacco plants, and the E. coli-expressed HrBP1 protein was assembled into oligomers by Q-R via binding to HrBP1 with a dissociation constant of 1.19 μM. We, therefore, concluded that Q-R activated the HrBP1 and PR-1a genes and enhanced the ability of HrBP1 to assemble in tobacco plants.

研究领域: 植物病理学 · 分子生物学 · 生物化学
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Journal of Functional Foods · 2016 · IF 3.973

Comparative analysis of multiple ingredients in Rosa roxburghii and R. sterilis fruits and their antioxidant activities

Jing-Yu He,Yuan-He Zhang,Na Ma,Xu-Lin Zhang,Meng-Hua Liu,Wei-Ming Fu

The functional and potential bioactive ingredients, including the elements, amino acids and phytochemicals, in Rosa roxburghii (RR) and R. sterilis (RS) fruits were analysed by ICP-OES and -MS, HPLC-UV, and LC-MS/MS, respectively, and were compared to elucidate the characteristics of their ingredients. The antioxidant activities of the ethanolic extracts of RR and RS fruits were evaluated using four different methods, including 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, hydroxyl radical scavenging activity, inhibition of β -carotene bleaching, and ferric reducing antioxidant power assays; the correlation between the ingredients and their antioxidant activities was assessed. Furthermore, principal component analysis was selected to differentiate between the intra- and interspecies variation of RR and RS fruits. The results showed that RR and RS fruits contained numerous nutritious and biological ingredients and exhibited antioxidant activities, but there were significant differences among the fruits. Nevertheless, RR and RS fruits are attractive materials to produce highly valuable, functional foods.

研究领域: 植物学 · 药理学 · 食品科学 · 分析化学
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KOREAN JOURNAL OF CHEMICAL ENGINEERING · 2021 ·Vol. 38 ·期 5 ·1066-1077 · IF 3.309

Regenerated coenzyme-based preparation of bienzyme-polymer nanoconjugates and their applications for the synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate

Lu Yuan,Dai Hongqian,Cheng Pengpeng,Shi Hanbing,Tang Lan,Sun Xingyuan,Ou Zhimin

A modular approach was applied for the synthesis of bienzyme-polymer nanoconjugates (nano-BECs) (50–70 nm) consisting of two enzymes (carbonyl reductase and glucose dehydrogenase) conjugated within a single universal polymer scaffold. The amount of the product ethyl (R)-2-hydroxy-4-phenylbutyrate (R-HPBE) with nano-BECs as the catalyst was 533 mM in a dibutyl phthalate-phosphate buffer (dibutyl phthalate-PB) biphasic system, while the amount of R-HPBE was 349 mM using carbonyl reductase-poly(acrylic acid) as the catalyst, indicating that the nano-BECs have an advantage for coenzyme regeneration. Compared with a single aqueous phase, the substrate treatment capacity was improved at the interface of the dibutyl phthalate-PB biphasic system. Under the optimal reaction conditions (35 °C, 40 h, dibutyl phthalate-PB 1: 1), nano-BECs can completely convert substrate into optically pure R-HPBE (enantiomeric excess (e.e.) >99.9%) in the organic-aqueous system.

研究领域: 生物催化 · 酶工程 · 纳米技术 · 有机合成
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ACS Nano · 2025 · IF 16

Glutathione-Responsive Metal–Organic-Framework-Derived MnxOy/(A/R)TiO2 Nanoparticles for Enhanced Synergistic Sonodynamic/Chemodynamic/Immunotherapy

Yilin Yang,Ning Wang,Zhihua Wang,Fei Yan,Zhan Shi,Shouhua Feng

Despite the potential of sonodynamic therapy (SDT) in treating malignant tumors, the lack of effective sonosensitizers has limited its clinical implementation. In this study, we explored the relationship between the heteroatom doping concentration in metal–organic frameworks and interface formation after pyrolysis by regulating the addition of manganese sources and successfully derived Z-scheme heterojunctions MnxOy/(A/R)TiO2 (MTO) in situ from MIL-125-NH2 (Ti/Mn). The electron transfer pathway introduced by interfacial contact promoted carrier separation and greatly preserved the effective redox components, significantly influencing the performance of reactive oxygen species generation. Upon reaching the tumor sites, MTO effectively depleted glutathione to alleviate the suppressive tumor environment, and the heterojunctions and MnxOy in MTO facilitated SDT and synergistic chemodynamic therapy (CDT), respectively, leading to enhanced immunogenic cell death (ICD). Furthermore, Mn2+ uptake by dendritic cells (DCs) and the tumor-associated antigens released due to ICD activated the stimulator of interferon genes pathway, which elicited a robust tumor-specific immune response by driving the maturation of DCs and the activation of T cells. In addition, the activated T cells secreted high levels of interferon-γ to enhance Mn3+/Mn2+-mediated ferroptosis in metastatic tumor cells. The combination of MTO-mediated synergistic therapy and PD-L1 checkpoint blockade exhibited vaccine-like functions, inducing stronger systemic immunity and durable immune memory to inhibit tumor progression, metastasis, and recurrence. To summarize, we synthesized a self-enhancing nanoplatform for synergistic SDT/CDT/immunotherapy using multifunctional MOF-derived Z-scheme heterojunctions. This study provides an experimental basis for amplifying the potential of sonosensitizers while optimizing SDT-mediated systemic immunity while avoiding interference caused by additional adjuvants.

研究领域: 癌症治疗 · 纳米技术 · 材料科学 · 免疫学
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