Journal of Natural Medicines最新文献

{"title":"Methoxyflavone glucosides and caffeoyl phenylethanoid glycoside from Lysionotus pauciflorus: their structures and anti-ferroptosis activity","authors":"Rena Takizawa,&nbsp;Tomoyo Minamizono,&nbsp;Daisuke Tsuji,&nbsp;Xiao-Jie Yan,&nbsp;Feng-Lai Lu,&nbsp;Xue-Rong Yang,&nbsp;Dian-Peng Li,&nbsp;Reiko Akagi,&nbsp;Yoshiki Kashiwada,&nbsp;Naonobu Tanaka","doi":"10.1007/s11418-024-01851-w","DOIUrl":"10.1007/s11418-024-01851-w","url":null,"abstract":"<div><p>Phytochemical investigation on the aerial parts of <i>Lysionotus pauciflorus</i> Maxim. (Gesneriaceae), a medicinal plant used in Guangxi Zhuang Autonomous Region, China, resulted in the isolation of 13 secondary metabolites including two methoxyflavones, six flavonoid glycosides, and five caffeoyl phenylethanoid glycosides. Among these, the chemical structures of previously undescribed metabolites (<b>1</b>–<b>3</b>) were elucidated to be nevadensin 7-<i>O</i>-<i>β</i>-D-glucopyranosyl-(1 → 2)-<i>β</i>-D-glucopyranoside (<b>1</b>), nevadensin 7-<i>O</i>-<i>β</i>-D-glucopyranosyl-(1 → 6)-<i>β</i>-D-glucopyranoside (<b>2</b>), and 2-(3,4-dihydroxyphenyl)ethyl-1-<i>O</i>-<i>β</i>-D-apiofuranosyl-(1 → 4)-<i>α</i>-L-rhamnopyranosyl-(1 → 3)-<i>β</i>-D-(6'-<i>O</i>-<i>E</i>-caffeoyl)glucopyranoside (<b>3</b>) by detailed spectroscopic and HPLC analyses. Inhibitory activity of isolated compounds against RSL3-induced ferroptosis on human hepatoma Hep3B cells were evaluated.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"196 - 203"},"PeriodicalIF":2.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New sesquiterpenes from the soft coral Litophyton arboreum","authors":"Amany Hamouda Mahmoud,&nbsp;Sabry A. H. Zidan,&nbsp;Mamdouh Nabil Samy,&nbsp;Abdallah Alian,&nbsp;Mahmoud A. A. Ibrahim,&nbsp;Mostafa Ahmed Fouad,&nbsp;Mohamed Salah Kamel,&nbsp;Katsuyoshi Matsunami","doi":"10.1007/s11418-024-01843-w","DOIUrl":"10.1007/s11418-024-01843-w","url":null,"abstract":"<div><p>Two new sesquiterpenes; 8α,11-dihydroxy-β-cyperon (<b>2</b>), and 5-<i>epi</i>-7α-hydroxy-( +)-oplopanone (<b>3</b>), were isolated from the soft coral <i>Litophyton arboreum,</i> together with nine known ones, including five sesquiterpenes; 11-hydroxy-8-oxo-β-cyperon (<b>1</b>), alismoxide (<b>4</b>), 5β,8β-epidioxy-11-hydroxy-6-eudesmene (<b>5</b>), chabrolidione B (<b>6</b>), 7-oxo-tri-nor-eudesm-5-en-4β-ol (<b>7</b>), two sterols; 7β-acetoxy-24-methyl-cholesta-5,24(28)-diene-3β,19-diol (<b>8</b>), nebrosteroid M (<b>9</b>), and two glycerol derivatives; chimyl alcohol (<b>10</b>) and batyl alcohol (<b>11</b>). The structures of the isolated compounds were characterized using spectroscopic techniques, predominately HR-ESI–MS, 1D, 2D-NMR, and ECD analyses. Compounds <b>1</b>–<b>11</b> were evaluated for their cytotoxic activity against three human cancer-cell lines (A549, MCF-7 and HepG2), and anti-leishmanial potential against the causal parasite, <i>Leishmania major.</i> Compounds <b>4</b>, <b>8</b>, and <b>9</b> exhibited potent cytotoxic activity against the A549 cell line (IC₅₀ = 17.0 ± 2.5, 13.5 ± 2.1, and 16.5 ± 1.3 μg/ml, respectively) as compared with the standard antitumor agent etoposide (IC₅₀ 28.4 ± 4.5 μg/ml). In addition, compound <b>9</b> exhibited remarkable cytotoxic activity against MCF-7 cell line (IC₅₀ = 24.7 ± 2.1 μg/ml: 22.2 ± 4.2 μg/mL for etoposide).</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"162 - 169"},"PeriodicalIF":2.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01843-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation","authors":"Hao Zhang,&nbsp;Xiaoyun Ding,&nbsp;Yumei Qiu,&nbsp;Mengdie Xie,&nbsp;Hu Wang,&nbsp;Tingting Li,&nbsp;Huiyun Bao,&nbsp;Si Huang,&nbsp;Yinhua Xiong,&nbsp;Xilan Tang","doi":"10.1007/s11418-024-01850-x","DOIUrl":"10.1007/s11418-024-01850-x","url":null,"abstract":"<div><p>Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from <i>Angelica dahurica</i>, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25 mg/kg twice weekly for 6 weeks), and found that both IMP (25 mg/kg and 12.5 mg/kg) and dexrazoxane 12.5 mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25 µg/mL relieved DOX (1 μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"95 - 106"},"PeriodicalIF":2.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angelic acid triggers ferroptosis in colorectal cancer cells via targeting and impairing NRF2 protein stability","authors":"Yongyi Cao,&nbsp;Yu Wang,&nbsp;Yueyang Li,&nbsp;Sihan Liu,&nbsp;Lizhe Wang,&nbsp;Li Zhou,&nbsp;Ting Zhu","doi":"10.1007/s11418-024-01849-4","DOIUrl":"10.1007/s11418-024-01849-4","url":null,"abstract":"<div><p>Ferroptosis is a unique programmed cell death driven by iron-dependent phospholipid peroxidation. Tumor cells that escape from the conventional therapies appear more sensitive to ferroptosis. Therefore, it is extremely urgent to find safe and efficient active ingredients that induce ferroptosis in tumor cells. Herein, we identified that angelic acid, as a potent anti-tumor active ingredient in <i>Angelica sinensis</i>, profoundly sensitizes CRC cells to ferroptosis via a natural compound library screen. We revealed that angelic acid treatment is sufficient to predispose CRC cells to ferroptosis phenotype, evidenced by malondialdehyde (MDA) accumulation, lipid peroxidation, and upregulation of ferroptosis-associated markers CHAC1 and PTGS2, which is abolished by ferroptosis inhibitor Fer-1. Moreover, the results of network pharmacology showed that NRF2 is critical for angelic acid-mediated CRC cell ferroptosis. Mechanistically, angelic acid exerted its ferroptosis induction via directly binding and facilitating the degradation of NRF2. In addition, the syngeneic mouse models revealed that angelic acid boosts CRC cell sensitivity to ferroptosis inducer sulfasalazine with essentially no toxicity in vivo. Collectively, our findings highlighted a previously unrecognized anti-tumor mechanism of angelic acid and represented an appealing therapeutic strategy for CRC treatment.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"82 - 94"},"PeriodicalIF":2.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven undescribed meroterpenoids from Sargassum siliquastrum and their inhibitory activity against amyloid β aggregation","authors":"Mitsuhiro Sekiguchi,&nbsp;Mafumi Horiuchi,&nbsp;Yuta Tozawa,&nbsp;Hideyuki Shigemori","doi":"10.1007/s11418-024-01847-6","DOIUrl":"10.1007/s11418-024-01847-6","url":null,"abstract":"<div><p>The inhibition of amyloid β (Aβ) aggregation and degradation of Aβ aggregates are promising approaches for treating and preventing Alzheimer’s disease. In our search for Aβ42 aggregation inhibitors, we isolated seven undescribed meroterpenoids, sargasilides A (<b>1</b>)‒G (<b>7</b>), from brown alga (<i>Sargassum siliquastrum</i>) collected at Noto Peninsula in Japan. We structurally elucidated the isolated meroterpenoids using spectroscopic data and evaluated their activities using Thioflavin T assay and transmission electron microscopy. Among the seven compounds isolated, sargasilide B had the strongest inhibitory activity. From the comparison of structure and activity, the geometric isomerism of olefins and length of isoprene side chains are important for the activity of meroterpenoids isolated from brown alga.</p><h3>Graphical abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"73 - 81"},"PeriodicalIF":2.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective impact of glycitin on memory impairment in a pentylenetetrazol-induced chronic epileptic rat model: insights into hippocampal histology, oxidative stress, and inflammation","authors":"Saghi Hakimi Naeini,&nbsp;Hassan Rajabi-Maham,&nbsp;Abdolkarim Hosseini,&nbsp;Vahid Azizi","doi":"10.1007/s11418-024-01846-7","DOIUrl":"10.1007/s11418-024-01846-7","url":null,"abstract":"<div><p>Epilepsy, characterized by recurrent seizures, often accompanies neurocognitive impairments and is associated with increased oxidative stress and inflammation. This study investigates the possible neuroprotective properties of glycitin, a soy isoflavone, on memory impairment, its impact on oxidative stress responses, and inflammatory gene expression in a chronic epileptic rat model induced by pentylenetetrazol (PTZ). Glycitin was administered at varying doses to evaluate its potential neuroprotective impact on memory, oxidative stress, and inflammation in this model. Behavioural assessments, memory retention and recall capabilities, histopathological examinations, measurements of oxidative stress biomarkers, and molecular assessments were employed for comprehensive evaluation. The results demonstrated that glycitin significantly improved memory impairment and reduced oxidative stress in epileptic rats. Additionally, glycitin treatment decreased the expression of <i>tumor necrosis factor-α</i> (<i>TNF-α</i>) and <i>nuclear factor kappa B</i> (<i>NF-κB</i>), indicating its potential to modulate the inflammatory response associated with epilepsy. These observations underscore the potential of glycitin as a therapeutic candidate for mitigating memory impairments linked to chronic epilepsy due to its antioxidant and anti-inflammatory properties, offering insights into novel avenues for the development of targeted interventions aimed at preserving cognitive function and ameliorating oxidative damage and inflammation in epileptic conditions.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"59 - 72"},"PeriodicalIF":2.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on the quality evaluation of crude drugs","authors":"Hiroyuki Fuchino","doi":"10.1007/s11418-024-01845-8","DOIUrl":"10.1007/s11418-024-01845-8","url":null,"abstract":"<p>As crude drugs are natural products, their quality may vary. However, the degradation of the active ingredients in the compositional changes that occur during processing and preparation also affects the medicinal properties of the Kampo formula, which uses herbal medicines; therefore, a detailed investigation of the effects of compositional changes during preparation is required. Plant constituents vary in content depending on the year of cultivation and the plant part; however, detailed studies have rarely been reported for some crude drugs. Liquid chromatography-nuclear magnetic resonance/mass spectrometry revealed the degradation process of saponins, which are unstable components of the crude drug “Achyranthes root.” The presence of diterpenes unstable with respect to drying temperature in the leaves of the crude drug “Leonurus herb” was revealed and their structures were elucidated. At the examination stage of the degradation process of perillaldehyde, the characteristic aromatic component of Perilla herb, it was elucidated that some specimens contained a small amount of perillaldehyde and that they contained more α-asarone. A trend toward lower ephedrine content was observed toward the tip of the above-ground branching of the Ephedra herb. Multivariate analysis was also introduced into the quality assessment of crude drugs and was established as a tool to identify bioactive compounds using the component diversity of crude drugs and to elucidate component differences due to the cultivation environment.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"15 - 27"},"PeriodicalIF":2.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01845-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142363932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical profile and biological activities of Lysiphyllum binatum (Blanco) de Wit","authors":"Surasak Kheawchaum,&nbsp;Sanit Thongnest,&nbsp;Jutatip Boonsombat,&nbsp;Paratchata Batsomboon,&nbsp;Chulabhorn Mahidol,&nbsp;Hunsa Prawat,&nbsp;Somsak Ruchirawat","doi":"10.1007/s11418-024-01844-9","DOIUrl":"10.1007/s11418-024-01844-9","url":null,"abstract":"<p><i>Lysiphyllum binatum</i> (Blanco) de Wit in the Fabaceae family, despite its traditional medicinal uses, has not been the subject of prior scientific inquiry into its chemical and biological profile. The dichloromethane and MeOH extracts of its roots exhibited notably similar antioxidant activity, while the dichloromethane extract of the vine stems showed aromatase inhibition. This study aimed to identify the bioactive components responsible for these activities. Chemical investigation of the roots led to the isolation of six new metabolites, named lysiphans A–F (<b>1</b>–<b>6</b>), along with eight known compounds (<b>7</b>–<b>14</b>). The vine stem yielded lysiphan C (<b>3</b>) and compound <b>7</b>, as well as five known isolates (<b>15</b>–<b>19</b>). The structures of these metabolites were determined through NMR spectral analysis, HRESIMS, quantum chemical calculations of NMR and ECD spectra, and Mosher’s modifications to establish their absolute configurations. The biogenetic relationships between the new compounds were proposed. Several of the isolates were evaluated for their antioxidant, anti-aromatase, and cytotoxic properties. Lysiphan B (<b>2</b>) exhibited significant antioxidant activity, with an IC₅₀ value of 28.8 ± 0.4 μM in the diphenyl picrylhydrazyl radical (DPPH) assay, 3.5 ± 0.2 μM in the xanthine/xanthine oxidase (XXO) assay, and 1.5 ± 0.0 ORAC units in oxygen radical absorbance capacity (ORAC) assay. Additionally, compounds <b>12</b>, <b>13</b>, and <b>16</b> exhibited very strong aromatase inhibitory activity with IC₅₀ values of 0.3 ± 0.2, 4.7 ± 0.1, and 0.9 ± 0.2 µM, respectively. Compound <b>16</b> also demonstrated strong ORAC activity of 1.9 ± 0.1 ORAC units.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"45 - 58"},"PeriodicalIF":2.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Azamollugin, a mollugin derivative, has inhibitory activity on MyD88- and TRIF-dependent pathways","authors":"Yuki Nakajima,&nbsp;Hitomi Nishino,&nbsp;Kazunori Takahashi,&nbsp;Alfarius Eko Nugroho,&nbsp;Yusuke Hirasawa,&nbsp;Toshio Kaneda,&nbsp;Hiroshi Morita","doi":"10.1007/s11418-024-01842-x","DOIUrl":"10.1007/s11418-024-01842-x","url":null,"abstract":"<p>Previously, we reported that azamollugin, an aza-derivative of mollugin, exhibited potent inhibitory activity on NO production in LPS-stimulated RAW 264.7 cells. Further investigations in this study revealed that azamollugin not only suppressed iNOS gene expression regulated by NF-κB, but also inhibited LPS-induced IFN-β expression, which is known to be regulated by IRF3. Azamollugin exhibited an inhibitory activity on LPS-induced IRAK1 activation, suggesting inhibitory effect on the MyD88-dependent pathway. Furthermore, azamollugin inhibited LPS-induced phosphorylation of IRF3 and its upstream factor, TBK1/IKKε, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR4. In addition, azamollugin also suppressed poly(I:C)-induced phosphorylation of TBK1 and IRF3, suggesting an inhibitory effect on the TRIF-dependent pathway via TLR3. These results suggest that azamollugin has inhibitory activity against both the MyD88-dependent and TRIF-dependent pathways, respectively.</p>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"36 - 44"},"PeriodicalIF":2.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrocyclizing-thioesterases in bacterial non-ribosomal peptide biosynthesis","authors":"Kenichi Matsuda","doi":"10.1007/s11418-024-01841-y","DOIUrl":"10.1007/s11418-024-01841-y","url":null,"abstract":"<div><p>Macrocyclization of peptides reduces conformational flexibilities, potentially leading to improved drug-like properties. However, side reactions such as epimerization and oligomerization often pose synthetic challenges. Peptide-cyclizing biocatalysts in the biosynthesis of non-ribosomal peptides (NRPs) have remarkable potentials as chemoenzymatic tools to facilitate more straightforward access to complex macrocycles. This review highlights the biocatalytic potentials of NRP cyclases, especially those of cis-acting thioesterases, the most general cyclizing machinery in NRP biosynthesis. Growing insights into penicillin-binding protein-type thioesterases, a relatively new group of trans-acting thioesterases, are also summarized.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":654,"journal":{"name":"Journal of Natural Medicines","volume":"79 1","pages":"1 - 14"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11418-024-01841-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}