APPLIED AND ENVIRONMENTAL MICROBIOLOGY
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2026
·Vol. 92
·期 2
·
IF 3.7
Yating Zou,Jinghui Zhou,Yongyi Zeng,Bishuang Chen,Lan Liu,Gang Xu
The development of sustainable biocatalytic processes for pharmaceutical synthesis represents a major goal in green chemistry. Ene-reductases (ERs) are attractive biocatalysts for asymmetric hydrogenation of activated alkenes, yet their industrial application is often constrained by limited substrate scope and stability. In this study, we explored the deep-sea sediment metagenome of the South China Sea and identified 41 putative ER genes, with 22 successfully solubly expressed in Escherichia coli. Biochemical characterization revealed broad substrate specificity, achieving up to 90% conversion for diverse α,β-unsaturated compounds. Notably, three enzymes (S2gene2614772, S2gene1139, and S2gene22028) exhibited exceptional adaptability, maintaining high activity over a wide pH range (5.5–8.5) and at low temperatures (15°C). However, none of the wild-type ERs showed significant activity toward the prochiral substrate 2-oxo-4-phenyl-3-butenoic acid, a key intermediate for angiotensin-converting enzyme inhibitors (ACEIs). Through directed evolution, we obtained a mutant (S2gene22028-G102S) with 30-fold enhanced activity, reaching 90% conversion at 10 mM substrate. Scale-up synthesis (5 mmol substrate) afforded 2-oxo-4-phenylbutyric acid (OPBA) at 11 mg/mL, demonstrating industrial potential. This study highlights marine metagenomes as valuable sources of novel ERs and provides an efficient biocatalytic route to ACEI precursors.
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Foods
·
2026
·Vol. 15
·期 2
·279
·
IF 5.1
Xin Lu,Cong Jia,Lixia Zhang,Xiaojing Sun,Guohui Song,Qiang Sun,Jinian Huang
To prepare and characterize low-bitter angiotensin-converting enzyme (ACE)-inhibitory peptides from sesame protein, a triple-enzyme hydrolysis system was optimized using mixture design and response surface methodology. The resulting hydrolysate was separated by ultrafiltration and medium-pressure chromatography, followed by identification through nano-liquid chromatography–electrospray ionization-tandem mass spectrometry. Finally, the mechanism of typical low-bitter ACE-inhibitory peptides was elucidated by molecular docking and molecular dynamics simulation. Results showed that the optimal enzyme activity ratio of 1:0.94:1.07 for Alcalase, trypsin, and Flavourzyme, combined with optimized hydrolysis conditions (E/S ratio of 126,793.03 nkat/g, pH 8.40, 4.82 h hydrolysis time, and 45 °C), resulted in a peptide yield of 93.19 ± 0.14%, ACE-inhibitory rate of 95.92 ± 0.23%, and bitter value of 3.15 ± 0.09. APQLGR and APWLR exhibited high ACE-inhibitory activity and minimal bitterness among the seventeen identified peptides. Although both peptides bound to the S1 pocket and Zn2+catalytic site of ACE, APWLR exhibited an additional interaction with the S2 pocket. Both peptides were predicted to antagonize the bitter taste receptor T2R14 by forming stable complexes with key residues, but two complexes exhibited distinct mechanisms of stabilization. This work demonstrates a method for producing dual-functional peptides from sesame protein, paving the way for their application in functional foods.
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ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Qing Chang,Ruimeng Wang,Jiaxing Wang,Yaseen Muhammad,Zhenxia Zhao,Zhenfei Feng,Zuqiang Huang,Yanjuan Zhang,Zhongxing Zhao
A N-doped hollow copolymer tube (NHCT) was fabricated via template-free one-pot asynchronous polymerization strategy. Discrepancies of monomer polymerization speed and their hydrophilic–hydrophobic interaction resulted in the assembly of a hollow tube having inner diameter and double wall thickness of ∼230 and 40 nm, respectively. The formation and growth mechanism of NHCT analyzed via advanced characterization revealed that the unique growth processes tuned a demarcating surface layer between inner (hydrophilic) and outer (hydrophobic) layers. The screening and recognition ability of NHCT were determined for two specific dipeptides (WW and RR) possessing great discrepancies in hydrophilicity and angiotensin converting enzyme inhibitory (ACE-I) activity. NHCT realized high adsorption capacity (1.57 mmol/g) and selectivity (∼1274) for hydrophilic dipeptide RR (low ACE-I activity) from the mixture of RR/WW. As a result, ACE-I activity for residual solution were enhanced about 4.1 times as compared to original solution from natural silkworm pupae protein hydrolysate. Awarding to these results and its facile and discerning ability, NHCT can be envisioned to be of great value for the separation of small functional peptides from a natural edible source.
研究领域:
材料科学
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生物化学
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2020
·
IF 4.192
Li Hao,Xinchang Gao,Tingyi Zhou,Jinxuan Cao,Yangying Sun,Yali Dang,Daodong Pan
Umami peptides can help reduce the salt content in foods while still maintaining a savory taste. Few studies have reported the bioactivity of umami peptides after consumption. We studied the bioactivities of 12 umami peptides after gastrointestinal digestion. Three umami peptides exhibited angiotensin I-converting enzyme (ACE) inhibitory and antioxidant activity after digestion. Six novel peptides were identified from digestion solutions of the peptides by HPLC-MS/MS. Among them, CC, CCNK, and HCHT had both ACE inhibitory activity (IC50 values were 9.81, 9.00, and 114.99 μM, respectively) and antioxidant activity (strong 1,1-Diphenyl-2-pycryl-hydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) free radical scavenging activities). AHSVRF had strong ACE inhibitory activity. These peptides increased the nitric oxide concentration and decreased the content of endothelin-1 in a medium of human umbilical vein endothelial cells in a dose-dependent manner. Experiments with damaged HepG2 cells showed that peptides CC, CCNK, and HCHT had antioxidant activity through their cytoprotective effects and by reducing the reactive oxygen species content. The results indicated that umami peptides may provide many health benefits after consumption.
研究领域:
食品科学
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营养学
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生物化学
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药理学
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Foods
·
2026
·Vol. 15
·期 13
·2396
·
IF 6
Huiling Huang,Zhichao Yang,Lin Ye,Xujie Hou,Yiming Jia,Shenghuizi Chen,Ying Huang
In this study,Apocynum venetumwas employed as the raw material to optimize protein extraction and enzymatic hydrolysis processes for the preparation of highly active angiotensin-converting enzyme (ACE)-inhibitory peptides, achieving an ACE inhibition rate of 92.34%. Multispectral analyses and microstructural characterization demonstrated that enzymatic hydrolysis induced the unfolding of protein secondary structures, resulting in a looser and more porous morphology enriched with characteristic amino acids. A total of 2567 peptide sequences were identified by LC–MS/MS, among which 18 potential bioactive peptides were screened. Molecular docking analysis revealed that these peptides interact with the active site of ACE primarily through hydrogen bonding and hydrophobic interactions, with WLRDFL exhibiting the strongest binding affinity. This study systematically elucidates the structural characteristics and antihypertensive molecular mechanisms of ACE-inhibitory peptides derived fromApocynum venetum, providing both theoretical insights and experimental support for the development of natural antihypertensive functional foods and the high-value utilization of this plant.
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FOOD CHEMISTRY
·
2026
·
IF 10.4
Kexin Liu,Jiajun Cui,Ke Xu,Jiaqi Zheng,Yixuan Xiao,Lin Chen,Sha Li,Jiyou Yang,Hongying Guo,Xin Wang,Fei Gao,Jie Li,Weiwei Huan
A novel magnetic nanoplatform integrating online proteolysis and specific affinity enrichment was constructed. • 61 novel ACE inhibitory peptides were efficiently discovered from Torreya grandis protein. • The identified peptide CGDDGY showed significant in vitro ACE inhibitory activity (37.43% at 800 μmol/L). • The strategy provides a generic and efficient approach for screening antihypertensive peptides from food proteins. Although chemically synthesized ACE inhibitors are effective, they frequently cause side effects like cough, hypotension, and angioedema, which limits their use in clinical settings. However, these drawbacks have spurred interest in exploring natural sources for novel ACE inhibitory compounds. In this study, we developed a magnetic Fe 3 O 4 nanoplatform capable of specifically recognizing ACE inhibitory peptides. This strategy was employed for the specific enrichment peptides with ACE-inhibitory activity derived from Torreya grandis protein digests. Using immobilized enzyme technology combined with computational docking evaluation, 61 peptides exhibiting ACE inhibition were successfully identified, five of which exhibited binding energies below −9 kcal/mol. Among them, CGDDGY showed the highest inhibition rate (37.43% at 800 μmol/L). This method overcomes the limitations of conventional separation approaches based on polarity or molecular weight, providing a promising pathway for developing food-derived antihypertensive agents and a technical paradigm for the precise screening of natural functional factors. Download: Download high-res image (353KB) Download: Download full-size image
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JOURNAL OF DAIRY SCIENCE
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2019
·
IF 3.082
S.N. Li,S.H. Tang,Q. He,J.X. Hu,J. Zheng
ABSTRACT This study investigated the effects of Lactobacillus plantarum (Lp) and Bifidobacterium animalis ssp. lactis (Ba) in co-cultures with Streptococcus thermophilus (St) on changes in the acidification profile, proteolytic activity, peptide production, in vitro antioxidant activity, and angiotensin-converting enzyme (ACE) inhibitory properties of fermented milks during 21 d of storage at 4°C. The pH values and proteolysis in all batches showed a gradual decrease and increase during storage, respectively. The ACE-inhibitory activity and total antioxidant capacity of all co-fermented milk samples followed a similar pattern, with maximum values on d 6 of storage. The St starter, in conjunction with Ba or Lp or both, enhanced proteolysis, peptide generation, and ACE-inhibitory and antioxidant activity, but decreased pH values compared with St alone. The St-Ba-Lp samples showed higher DPPH • (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity, hydroxyl radical scavenging activity, and total antioxidant capacity, but similar superoxide anion scavenging activity compared to St-Ba or St-Lp samples. The St-Ba samples showed higher DPPH • radical scavenging activity but lower hydroxyl radical scavenging activity than St-Lp samples. In the ACE-inhibitory assays, the St-Lp samples exhibited relatively low activity among the co-fermented milks, digested or not. The presence of Ba and Lp in fermentation together did not affect ACE-inhibitory activity in undigested fermented milks compared with the presence of Ba alone, and St-Ba-Lp fermented milks demonstrated an increase in ACE-inhibitory activity after simulated gastrointestinal digestion in storage. Pepsin digestion largely improved ACE-inhibitory activity, except in St-Lp samples, in which the activity was reduced. Further hydrolysis by trypsin reduced final activity in digestion. This study suggests that co-cultured fermentation with probiotics improves in vitro antioxidant and ACE inhibition activity in fermented milks, and this effect is partly due to the higher proteolytic activity of probiotics.
研究领域:
食品科学
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微生物学
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生物化学
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Food Bioscience
·
2024
·
IF 4.8
Xin-Yu Zu,Ya-Nan Zhao,Yan Liang,Ying-Qiu Li,Chen-Ying Wang,Xiang-Zhong Zhao,Hua Wang
The rapid screening of angiotensin I-converting enzyme (ACE) inhibitory peptides (ACEIPs) from protein hydrolysates remains a challenge in current researches. The current study presents the development of an efficient affinity medium (AOPAN–ACE) consisting of ACE immobilized on the surface of electrostatically spun polyacrylonitrile nanofibrous membranes for the efficient screening of ACEIPs. The application of this affinity medium followed by liquid chromatography–tandem mass spectrometry analysis resulted in the successful screening and identification of 60 potential ACEIPs from protein hydrolysates of tuna dark muscle. Notably, the application of PeptideRanker, pLM4ACE, and molecular docking approaches resulted in the screening and identification of a novel ACEIP FPPDVA. Furthermore, the peptide FPPDVA was synthesized using the solid-phase method, and its IC 50 value on ACE was determined to be 87.11 ± 1.02 μM. Molecular docking analysis suggested that the ACEIP of the peptide FPPDVA is attributable to the formation of hydrogen bonds with the S1 active site (Ala354 and Tyr523) of ACE and metal–ligand bonds with Zn 2+ . In addition, molecular dynamics simulations revealed that the peptide FPPDVA formed a stable complex with ACE and was consistently localized within the active pocket of ACE over a simulation duration of 100 ns without being displaced from the active site. Lineweaver–Burk analysis further confirmed that the peptide FPPDVA exhibited mixed mode of inhibition against ACE. Overall, the affinity medium developed in the current study is potentially useful for highly efficient screening of ACEIPs, and the novel ACEIP FPPDVA identified herein is a promising functional food ingredient for antihypertensive application.
研究领域:
食品科学
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生物化学
·
药物开发
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Food Biophysics
·
2026
·Vol. 21
·期 2
·64
·
IF 3.9
Barido Farouq Heidar,Chan Kok-Gan,Tirtadanu,Chua Kah Ooi,Wahyono Teguh,Utama Dicky Tri,Lee Sung Ki
This study aimed to evaluate the combined effects of enzymatic hydrolysis and drying methods on functional attributes, nutritional contents, bioactive compounds and antioxidant capacity of black garlic ( Allium sativum L .). Three proteolytic enzymes with distinct protease activity namely Alcalase, Pepsin, and Flavorzyme were applied to five different drying treatments: sun drying (SDry), hot air drying (HDry), freeze drying (FDry), infrared-assisted freeze drying (IFDry) and pulsed vacuum drying (PVDry). This study demonstrated that Alcalase exhibited the highest proteolytic efficiency showing the highest degree of hydrolysis at 50.47% ( p < 0.05), total soluble protein at 150.76 µg/mL ( p < 0.05), and a significantly higher total sugar content ( p < 0.05). Notably, PVDry preserved these parameters better than thermal methods, highlighting its efficacy in minimizing oxidative and thermal degradation. Enhanced levels of key amino acids including hydrophobic, aromatic, and sulfur-containing residues were linked to increased antioxidant, metal-chelating, nitric oxide scavenging, and ACE-inhibitory activities. PVDry-Alcalase treatments consistently showed the most pronounced functional improvements. Phenolic and flavonoid contents were also elevated in non-thermal drying combined with enzymatic hydrolysis, further enhancing radical scavenging capacities. This study demonstrates that integrating broad-specificity enzymatic hydrolysis with mild drying techniques strategically maximizes black garlic’s bioactive compound extraction and stability, underpinning its potential as a potent functional food ingredient. These findings provide a methodological framework for optimizing industrial black garlic production to improve health-promoting properties and product quality.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2019
·Vol. 100
·期 1
·315-324
·
IF 2.422
Jiali Chen,Bomi Ryu,YuanYuan Zhang,Peng Liang,Chengyong Li,Chunxia Zhou,Ping Yang,Pengzhi Hong,Zhong-Ji Qian
BACKGROUND In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC 50 = 2.577 μmol L −1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver–Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION LSGYGP, with an IC 50 value of 2.577 μmol L −1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry
研究领域:
食品科学
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药理学
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生物化学
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Science China-Life Sciences
·
2023
·
IF 9.1
Tang Kegong,Wang Xiaona,Zhao Yu,Li Xiaobei,Jiang Zhenyu,Mei Song,Chen Mingrui,Ma Yiming,Du Xinyi,Qiao Xiangyu,Sun Na,Liu Jiaqi,Jiang Chengyu
Hypertension has become a growing public health concern worldwide. In fact, hypertension is commonly associated with increased morbidity and mortality. Currently, oligonucleotide drugs have proven to be promising therapeutic agents for various diseases. In the present study, we aimed to demonstrate that a herbal small RNA (sRNA), XKC-sRNA-h3 (B55710460, F221. I000082.B11), exhibits potent antihypertensive effects by targeting angiotensin-converting enzyme (ACE) in mice. When compared with captopril, oral administration of the sphingosine (d18:1)-XKC-sRNA-h3 bencaosome more effectively prevented angiotensin II-induced hypertensive cardiac damage and alleviated kidney injury in mice. Such findings indicated that XKC-sRNA-h3 may be a novel orally available ACE inhibitor type oligonucleotide drug for hypertension.
研究领域:
药理学
·
分子生物学
·
心血管研究
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Analytical Methods
·
2020
·Vol. 12
·期 48
·5833-5838
·
IF 2.596
Zheng Yuan,Peng Xu,Fangzhi Yu,Dapeng Zhang,Qiang Zhao,Wenqiang Yu,Hailin Wang
Affinity Capillary Electrophoresis (ACE) is a useful analytical tool to study noncovalent interactions. However, it remains challenging for ACE to measure weak and unstable interactions due to the fast dissociation of the binding complex and the possible destruction of the complex by a high electric field. In this study, we proposed a two-direction migration strategy that enables ACE to detect weak and unstable but important interactions by decreasing the migration distance of the binding complex and controlling the opposite migration direction of the free probe. By synthesizing a polyacrylamide-coated neutral capillary, free of electroosmotic flow, two-direction CE migration of basic peptides (positively charged) and peptide–RNA complexes (negatively charged) was achieved. Furthermore, the weak interactions between small nuclear U2 RNA and histone peptides were detected by this two-direction migration CE approach. The effects of the methylation states of histone peptides on the weak peptide–RNA interactions were also explored by this new approach. Collectively, the suggested modification of the ACE method is able to qualitatively characterize weak interactions.
研究领域:
分析化学
·
生物化学
·
分子生物学
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