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Cell Reports Medicine · 2026 · IF 14

Commensal Cutibacterium acnes-derived indolelactic acid safeguards skin barrier function through the aryl hydrocarbon receptor

Shan Zhang,Fang Li,Xiaoqiang Xu,Tianze Yu,Yang Liu,Xiaokai Fang,Yuan Zhou,Beilei Xu,Yu Zhang,Yang Luo,Qianjin Lu,Xiaochun Liu,Wei Li,Xu Yao

Skin microbial dysbiosis is a key characteristic of atopic dermatitis (AD). Although Cutibacterium acnes ( C. acnes ) is the most abundant bacterium in the skin microbiota, its precise functions in AD remain unclear. Here, whole-genome sequencing of C. acnes isolates reveals strain-level genomic and functional heterogeneity between AD patients and healthy individuals. Metabolomic profiling identifies reduced indolelactic acid (ILA), a tryptophan metabolite, in AD skin and in cultures of AD-associated C. acnes strains . In murine models of epidermal-barrier-damaged and AD-like dermatitis, topical ILA application activates the aryl hydrocarbon receptor (AhR) pathway in keratinocytes, upregulating tight junction proteins and suppressing interleukin (IL)-33 to restore barrier integrity and mitigate dermatitis. A proof-of-concept clinical trial confirms ILA’s efficacy in reducing transepidermal water loss and alleviating AD symptoms. Our study establishes C. acnes -derived ILA as a crucial regulator of skin barrier repair via AhR signaling, offering therapeutic potential for AD. Clinical trial registration: ChiCTR2400090988.

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Synthetic and Systems Biotechnology · 2026 · IF 4.4

Biosynthesis of patchoulol via metabolic engineering the oleaginous red yeast Rhodotorula toruloides

Xiaochun Zheng,Yajun Li,Zhenhua Liu,Peng Sun,Yaqi Dong,Xue Wang,Yanan Wang,Xiaobing Yang

Patchoulol is a widely used sesquiterpenoid in perfumes, cosmetics, foods and pharmaceuticals. The plant-dependent production is suffering from limited growing area, long seasonal cycle, etc. Microbial production represents a sustainable alternative as it is featured with mild operating conditions and eco-friendliness. Herein, we engineered the oleaginous Rhodotorula toruloides toward patchoulol production. First, the patchoulol biosynthesis baseline was constructed by employing a chimeric enzyme of the Pogostemon cablin originated patchoulol synthase and the native FPPS. Second, the supply of essential intermediates was streamlined by redeploying the mevalonate (MVA) pathway while the recycling of NADPH was enhanced through over-expressing related enzymes. Third, the patchoulol production was further enhanced to 724.8 mg/L, 6.0 mg/L/h and 36.2 mg/g glucose by down-regulating the squalene biosynthesis and tuning the cultivation condition in shake flask. Finally, the production of patchoulol was increased to 1.31 g/L and 13.8 mg/g glucose in the minimal medium in a 3-L bioreactor. Our study demonstrated the potential of R. toruloides in producing patchoulol, and should shed light on the microbial synthesis of other sesquiterpenes.

CAS / MDL: 111-02-4 5986-55-0
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BIORESOURCE TECHNOLOGY · 2026 · IF 8.2

A dCas9-integrated iLight9O system enables dynamic regulation for enhanced patchoulol biosynthesis in Saccharomyces cerevisiae

Li Li,Yasen Wang,Buqing Wang,Liqun Shen,Yahui Gao,Wei Lin,Zijie Li

Numerous organisms have evolved the ability to utilize light through photoreceptor proteins that mediate diverse biological processes. Currently, several optogenetic sensor systems are widely used in yeast. However, when these systems are applied for gene repression to regulate endogenous yeast gene expression, they typically require the insertion of corresponding target sites near the native promoter of the gene of interest to achieve precise modulation. To address these constraints, a novel blue light-inducible optogenetic tool designated iLight9 was developed, a single-component optogenetic biosensor integrated with the CRISPR-dCas9 platform. The stability of the iLight9 system was further enhanced by employing a strategy involving the addition of a protein degradation tag. The resulting system was designated as iLight9O, which facilitated programmable regulation of distinct genes through the introduction of specific sgRNAs. Subsequently, systematic metabolic engineering strategies were employed to construct an efficient patchoulol-producing cell factory in Saccharomyces cerevisiae . Moreover, a two-step isoprenol utilization (IU) pathway was introduced into the recombinant strain to enhance its capacity for patchoulol biosynthesis. Crucially, the iLight9O system was adopted to dynamically downregulate squalene synthase, a key enzyme in the competing squalene biosynthetic pathway. This optogenetic flux control strategy increased patchoulol titers by 66 % in the IU-optimized strain and 24 % in the MVAIU2 strain, demonstrating significant improvements over static engineering approaches.

CAS / MDL: 111-02-4 5986-55-0
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Journal of Oleo Science · 2022 · IF 1.628

Efficient Ultrasonic-assisted Aqueous Enzymatic Method for Pecan Nut Kernel Oil Extraction with Quality Analysis

Anning Liu,Huijuan Jing,Xiaojing Du,Chaoyang Ma,Hongxin Wang

In this study, the recovery of pecan nut kernel oil (PNKO) obtained by mechanical pressing (MP) was compared with that obtained by ultrasonic-assisted aqueous enzymatic extraction (UAAEE). At the same time, contents of substances with proven bioactivity, fatty acid compositions, physicochemical properties and antioxidant activities of PNKO were also assessed. Obviously, the oil yield obtained by UAAEE (71.32%) was higher than that obtained by MP (56.81%). Therefore, Plackett-Burman design (PBD), as well as Box-Behnken design (BBD), further optimized the UAAEE process, and the highest oil yield of 78.83% was acquired under the following conditions: incubation time of 2 h, the mixed enzyme (cell ulase+hemicellulase+pectinase+neutrase, w/w/w/w=1/1/1/1) concentration of 2.9%, liquid-solid ratio of 4 mL/g, pH of 4, particle size of 300 μm, ultrasonic time of 20 min, ultrasonic power of 432 W and reaction temperature of 53°C. The PNKO obtained by the two methods possessed similar fatty acid composition, but that obtained by UAAEE had comparatively low acid value and peroxide value. Moreover, rich content of total phenolics, squalene and phytosterols, as well as strong scavenging activities against DPPH and ABTS+ free radicals, were also contained in the PNKO obtained by UAAEE. These results demonstrated that UAAEE was an efficient method to acquire pecan nut kernel oil with excellent quality and high recovery.

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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS · 2023 · IF 5.2

Amphiphilic O(Phe-r-Glu) oligopeptides randomly polymerized via papain exhibiting a pH-insensitive emulsification property

Feng Wang,Chao Li,Haohao Wang,Lu Yu,Fuming Zhang,Robert J. Linhardt

Natural amino acid polymers have been wide-used as bio-compatible emulsion stabilizers . In this study, Amphiphilic O(Phe- r -Glu)s were synthesized through the papain-catalyzed random polymerization of L -phenylalanine and L -glutamate with the major degree of polymerization value of 6–7. The polymerization yield was increased by more than 35 % using choline to reduce the energy barrier for the amino substrates to form the tetrahedral intermediate with the catalytic triad. The squalene/water emulsions stabilized by O(Phe- r -Glu) nanoparticles were pH-insensitive at pH 1–12. The investigation of mechanism found the combined effects of steric hindrance , electrostatic repulsion and the viscosity of the emulsion contributed to the stability of the emulsion droplets. Under acidic condition, the layers of O(Pho- r -Glu)s particle aggregates formed around the emulsion droplets and the higher viscosity of emulsion mainly contributed to the stability of emulsions . At basic condition, the strong electrostatic repulsion between emulsion droplets covered by the negatively charged O(Pho- r -Glu) particles and the steric hindrance contributed mainly to the prevention of the coalescence of emulsion droplets. The application of enzymatically synthesized amphiphilic peptides in emulsion, along with tunable performance through the polymerization of amino substrates, is in line with the sustainable development requirements in fields such as pharmaceuticals, food and cosmetics.

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Frontiers in Bioengineering and Biotechnology · 2022 · IF 6.064

Developing Smart Nanoparticles Responsive to the Tumor Micro-Environment for Enhanced Synergism of Thermo-Chemotherapy With PA/MR Bimodal Imaging

Luo Mingfang,Lv Yijie,Luo Xunrong,Ren Qingfa,Sun Zhenbo,Li Tianping,Wang Ailing,Liu Yan,Yang Caixia,Li Xianglin

With the development of nanotechnology, a theranostics nanoplatform can have broad applications in multimodal image-guided combination treatment in cancer precision medicine. To overcome the limitations of a single diagnostic imaging mode and a single chemotherapeutic approach, we intend to combat tumor growth and provide therapeutic interventions by integrating multimodal imaging capabilities and effective combination therapies on an advanced platform. So, we have constructed IO@MnO2@DOX (IMD) hybrid nanoparticles composed of superparamagnetic iron oxide (IO), manganese dioxide (MnO2), and doxorubicin (DOX). The nano-platform could achieve efficient T2-T1 magnetic resonance (MR) imaging, switchable photoacoustic (PA) imaging, and tumor microenvironment (TME)-responsive DOX release and achieve enhanced synergism of magnetic hyperthermia and chemotherapy with PA/MR bimodal imaging. The results show that IMD has excellent heating properties when exposed to an alternating magnetic field (AMF). Therefore, it can be used as an inducer for tumor synergism therapy with chemotherapy and hyperthermia. In the TME, the IMD nanoparticle was degraded, accompanied by DOX release. Moreover, in vivo experimental results show that the smart nanoparticles had excellent T2-T1 MR and PA imaging capabilities and an excellent synergistic effect of magnetic hyperthermia and chemotherapy. IMD nanoparticles could significantly inhibit tumor growth in tumor-bearing mice with negligible side effects. In conclusion, smart IMD nanoparticles have the potential for tumor diagnosis and growth inhibition as integrated diagnostic nanoprobes.

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Polymers · 2022 ·Vol. 14 ·期 12 ·2410 · IF 4.967

Preparation of Cellulose-Based Flocculant and Its Application in the Enrichment of Vitamin K2 in Fermentation Supernatant

Guoliang Ma,Zhiming Zheng,Han Wang,Li Wang,Genhai Zhao,Hengfang Tang,Xiumin Ding,Peng Wang

Nutritional food supplements and pharmaceutical products produced with vitamin K2as raw materials a very promising market in the global scope. The main production method of vitamin K2is microbial fermentation, but approximately 50% of vitamin K2synthesized by the main production strainBacillus subtilis nattoexists in extracellular form, which is not easy to separate and extract. In order to solve this problem, in this study, we synthesized a novel cellulose flocculant, MCC-g-LMA, by grafting reaction using microcrystalline cellulose (MCC) and lauryl methacrylate (LMA) as monomers, and ammonium persulfate as an initiator to flocculate VK2from the fermentation supernatant. The flocculant was characterized by Fourier transform infrared spectroscopy (FTIR), elemental analysis, and scanning electron microscopy (SEM), and the grafting reaction was successful. When the flocculant dosage was 48.0 mg/L and pH was 5.0, the flocculation rate of the MCC-g-LMA on the fermentation supernatant reached 85.3%, and the enrichment rate of VK2reached 90.0%. Furthermore, we explored the flocculation mechanism of VK2by the MCC-g-LMA and speculated that the flocculation mechanism mainly included adsorption bridging, hydrophobic association and net trapping and sweep effect. In this study, the extraction method for trace high-value biological products in the fermentation supernatant was improved, which provided a method and theoretical basis for the efficient separation and purification of VK2and other terpenoids.Keywords:cellulose;flocculant;Bacillus subtilis nattofermentation supernatant;vitamin K2

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FOOD CHEMISTRY · 2021 · IF 7.514

Evaluation of trans fatty acids, carbonyl compounds and bioactive minor components in commercial linseed oils

Zihan Xu,Shanshan Liu,Mingyue Shen,Jianhua Xie,Jun Yang

Trans fatty acids (TFAs), associated with the risks of coronary heart disease and diabetes, are formed by isomerization of unsaturated fatty acids during refining of linseed oils. In this study, TFAs and the chemical characteristics (acid value, peroxide value, carbonyl compounds, bioactive minor components and fatty acids) in 32 commercial linseed oils were investigated, and the correlation among them were further analyzed. Results showed that C18:3 TFAs were predominant TFAs in linseed oils and about 9% of the samples had TFA contents above 2 g/100 g fat, as well as the average level of TFA in the refined samples was higher than that in the unrefined oils. The correlation analyses suggested C18:3 TFAs exhibited significant negative correlations with acid value, levels of acetone, trans -2-nonenal, campesterol and α-linolenic acid. These results provided a comprehensive insight of TFAs in linseed oil and had important implications for consumers and linseed oil industry.

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Food Analytical Methods · 2021 ·Vol. 14 ·期 8 ·1567-1576 · IF 3.366

Simultaneous Determination of Tocopherols, Phytosterols, and Squalene in Vegetable Oils by High Performance Liquid Chromatography-Tandem Mass Spectrometry

Liu Shanshan,Hu Huiyu,Yu Yanpeng,Zhao Jiahui,Liu Lichun,Zhao Shanshan,Xie Jianhua,Li Chang,Shen Mingyue

Vegetable oil is one of the principal sources of minor bioactive substances such as tocopherol, phytosterol, and squalene. In order to obtain the distribution of these substances in vegetable oil, this study developed and validated high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method for the simultaneous analysis of tocopherols (α-, β-, γ-, and δ-tocopherol), phytosterols (β-sitosterol, stigmasterol, brassicasterol, and campesterol), and squalene in vegetable oils. An automatic gel permeation chromatography (GPC) system was used to remove triglycerides from oils, avoiding the heat treatment of traditional saponification. Method validation revealed the accuracy and reliability of this method. The current approach achieved the successful separation of β- and γ-tocopherol, which solved the problem of coelution and inaccurate quantification for β- and γ-tocopherol in previous study. Additionally, this method was applied to detect tocopherols, phytosterols, and squalene in 9 categories of vegetable oils.

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ACS Applied Materials & Interfaces · 2021 · IF 9.229

Fluorescent Cationic Conjugated Polymer-Based Adaptive Developing Strategy for Both Sebaceous and Blood Fingerprints

Chi Zhang,Zhinan Fan,Hao Zhan,Hong Zhou,Rongliang Ma,Li-Juan Fan

Both latent sebaceous and blood fingerprints may provide valuable information for forensic investigation. To detect both types of fingerprints with no need to predistinguish them, a new adaptive developing strategy was proposed. A cationic conjugated polymer with poly[p-(phenylene ethylene)-alt-(thienylene ethynylene)] backbone (PPETE-NMe3+) was synthesized, which was dissolved in N,N-dimethylformamide (DMF) to form the developing solution. Fingerprints were developed by a simple dropping and incubating process without any pre-/post-treatments. Fluorescent photographs of the developed fingerprints on various substrates demonstrated that this developing strategy was effective for both types of fingerprints on nonporous substrates. Gray value analysis further confirmed the enhancement of the legibility of the fingerprint images. The preliminary mechanism exploration suggested that certain weak interactions, such as hydrophobic interaction and electrostatic interaction, may synergistically contribute to the interaction between the polymer and fingerprint components. The molecular design of the polymer combined with an appropriate solvent endowed the developing system the adaptiveness toward different types of fingerprints. This adaptive developing strategy made the fingerprint-developing process more efficient and may be further extended to more practical application scenes.

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2020 · IF 4.192

Metabolic Engineering of Saccharomyces cerevisiae To Overproduce Squalene

Tian Li,Guo-Song Liu,Wei Zhou,Min Jiang,Yu-Hong Ren,Xin-Yi Tao,Min Liu,Ming Zhao,Feng-Qing Wang,Bei Gao,Dong-Zhi Wei

Squalene has wide applications in the food and pharmaceutical industries. Engineering microbes to produce squalene is a promising alternative for traditional production approaches. In this study, squalene production was enhanced to 978.24 mg/L through stepwise overexpression of the enzymes that catalyze acetyl-CoA to squalene. Subsequently, to increase the activity of HMG-CoA reductase and alleviate the high dependence on NADPH, the HMG-CoA reductase (NADH-HMGR) from Silicibacter pomeroyi, highly specific for NADH, was introduced, which increased squalene production to 1086.31 mg/L. Native ethanol dehydrogenase ADH2 and acetaldehyde dehydrogenase ADA from Dickeya zeae were further overexpressed, which enhanced the capability to utilize ethanol for squalene synthesis and endowed the engineered strain with greater adaptability to high ethanol concentrations. Finally, a remarkable squalene production of 9472 mg/L was obtained from ethanol via carbon source-controlled fed-batch fermentation. This study will greatly accelerate the process of developing microbial cell factories for squalene production.

CAS / MDL: 111-02-4
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BIOCHEMICAL ENGINEERING JOURNAL · 2020 · IF 3.475

Improved linalool production in Saccharomyces cerevisiae by combining directed evolution of linalool synthase and overexpression of the complete mevalonate pathway

Pingping Zhou,Yi Du,Nannan Xu,Chunlei Yue,Lidan Ye

With special fragrance and various biological properties, linalool has wide applications in food, pharmaceuticals and cosmetics industries. Microbial biosynthesis has become a promising approach to linalool production, however its efficiency is limited by the limited precursor supply and poor efficiency of linalool synthase. With the goal of enhancing heterologous linalool production in Saccharomyces cerevisiae , protein engineering and metabolic engineering were simultaneously employed to solve these bottlenecks. Linalool-producing yeast was first constructed by introduction of t67OMcLIS selected out from a collection of linalool synthases. The efficiency of linalool biosynthesis was then improved by strengthening the supply of geranyl pyrophosphate (GPP) as precursor via overexpression of the complete mevalonate (MVA) pathway and a GPP synthase variant. To accelerate the conversion of the accumulated GPP to linalool, t67OMcLIS was engineered by means of directed evolution after development of a competition-based color-indicated high-throughput screening method. Expression of the t67OMcLIS variant in the engineered S. cerevisiae with enhanced precursor supply yielded 53.14 mg/L of linalool in biphasic shake-flask culture. This study delivered an efficient linalool-producing yeast cell factory and meanwhile provided efficient strategies for biosynthesis of other valuable monoterpenes.

CAS / MDL: 111-02-4
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