Pub Date : 2024-05-02DOI: 10.1021/acs.jnatprod.3c00867
Eduardo J. Caro-Diaz*, Marcy J. Balunas*, Lesley-Ann Giddings, Sandra Loesgen, Brian T. Murphy, C. Benjamin Naman, Christine E. Salomon, Kevin J. Tidgewell and Jaclyn M. Winter,
Scientific conferences and meetings are valuable opportunities for researchers to network, communicate, and develop knowledge. For early career scientists, conferences can also be intimidating, confusing, and overwhelming, especially without having adequate preparation or experience. In this Perspective, we provide advice based on previous experiences navigating scientific meetings and conferences. These guidelines outline parts of the hidden curriculum around preparing for and attending meetings, navigating conference sessions, networking with other scientists, and participating in social activities while upholding a recommended code of conduct.
{"title":"Outlining the Hidden Curriculum: Perspectives on Successfully Navigating Scientific Conferences","authors":"Eduardo J. Caro-Diaz*, Marcy J. Balunas*, Lesley-Ann Giddings, Sandra Loesgen, Brian T. Murphy, C. Benjamin Naman, Christine E. Salomon, Kevin J. Tidgewell and Jaclyn M. Winter, ","doi":"10.1021/acs.jnatprod.3c00867","DOIUrl":"10.1021/acs.jnatprod.3c00867","url":null,"abstract":"<p >Scientific conferences and meetings are valuable opportunities for researchers to network, communicate, and develop knowledge. For early career scientists, conferences can also be intimidating, confusing, and overwhelming, especially without having adequate preparation or experience. In this Perspective, we provide advice based on previous experiences navigating scientific meetings and conferences. These guidelines outline parts of the hidden curriculum around preparing for and attending meetings, navigating conference sessions, networking with other scientists, and participating in social activities while upholding a recommended code of conduct.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jnatprod.3c00867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1021/acs.jnatprod.4c00237
Yaodong Ning, Qinwufeng Gu, Te Zheng, Yao Xu, Song Li, Yuping Zhu, Bo Hu, Haobing Yu, Xiaoyu Liu, Yun Zhang, Binghua Jiao and Xiaoling Lu*,
With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain Eutypella sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound 7 possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds 6, 8, 11, 14, and 15 exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene 8 inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound 8 also alleviated the CuSO4-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.
{"title":"Genome Mining Leads to Diverse Sesquiterpenes with Anti-inflammatory Activity from an Arctic-Derived Fungus","authors":"Yaodong Ning, Qinwufeng Gu, Te Zheng, Yao Xu, Song Li, Yuping Zhu, Bo Hu, Haobing Yu, Xiaoyu Liu, Yun Zhang, Binghua Jiao and Xiaoling Lu*, ","doi":"10.1021/acs.jnatprod.4c00237","DOIUrl":"10.1021/acs.jnatprod.4c00237","url":null,"abstract":"<p >With the advancement of bioinformatics, the integration of genome mining with efficient separation technology enables the discovery of a greater number of novel bioactive compounds. The deletion of the key gene responsible for triterpene cyclase biosynthesis in the polar strain <i>Eutypella</i> sp. D-1 instigated metabolic shunting, resulting in the activation of dormant genes and the subsequent production of detectable, new compounds. Fifteen sesquiterpenes were isolated from the mutant strain, with eight being new compounds. The structural elucidation of these compounds was obtained through a combination of HRESIMS, NMR spectroscopy, and ECD calculations, revealing six distinct skeleton types. Compound <b>7</b> possessed a unique skeleton of 5/10 macrocyclic ether structure. Based on the gene functions and newly acquired secondary metabolites, the metabolic shunting pathway in the mutant strain was inferred. Compounds <b>6</b>, <b>8</b>, <b>11</b>, <b>14</b>, and <b>15</b> exhibited anti-inflammatory effects without cytotoxicity through the release of nitric oxide from lipopolysaccharide-stimulated RAW264.7 cells. Notably, acorane-type sesquiterpene <b>8</b> inhibited nitric oxide production and modulated the MAPK and NLRP3/caspase-1 signaling pathways. Compound <b>8</b> also alleviated the CuSO<sub>4</sub>-induced systemic neurological inflammation symptoms in a transgenic fluorescent zebrafish model.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1021/acs.jnatprod.3c00993
Young Eun Du, Jinsheng Cui, Eunji Cho, Sunghoon Hwang, Yong-Joon Jang, Ki-Bong Oh, Sang-Jip Nam and Dong-Chan Oh*,
Serratiomycin (1) is an antibacterial cyclic depsipeptide, first discovered from a Eubacterium culture in 1998. This compound was initially reported to contain l-Leu, l-Ser, l-allo-Thr, d-Phe, d-Ile, and hydroxydecanoic acid. In the present study, 1 and three new derivatives, serratiomycin D1–D3 (2–4), were isolated from a Serratia sp. strain isolated from the exoskeleton of a long-horned beetle. The planar structures of 1–4 were elucidated by using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparison of the NMR chemical shifts and the physicochemical data of 1 to those of previously reported serratiomycin indeed identified 1 as serratiomycin. The absolute configurations of the amino units in compounds 1–4 were determined by the advanced Marfey’s method, 2,3,4,6-tetra-O-acetyl-β-d-glucopyranosyl isothiocyanate derivatization, and liquid chromatography–mass spectrometric (LC–MS) analysis. Additionally, methanolysis and the modified Mosher’s method were used to determine the absolute configuration of (3R)-hydroxydecanoic acid in 1. Consequently, the revised structure of 1 was found to possess d-Leu, l-Ser, l-Thr, d-Phe, l-allo-Ile, and d-hydroxydecanoic acid. In comparison with the previously published structure of serratiomycin, l-Leu, l-allo-Thr, and d-Ile in serratiomycin were revised to d-Leu, l-Thr, and l-allo-Ile. The new members of the serratiomycin family, compounds 2 and 3, showed considerably higher antibacterial activities against Staphylococcus aureus and Salmonella enterica than compound 1.
{"title":"Serratiomycins D1–D3, Antibacterial Cyclic Peptides from a Serratia sp. and Structure Revision of Serratiomycin","authors":"Young Eun Du, Jinsheng Cui, Eunji Cho, Sunghoon Hwang, Yong-Joon Jang, Ki-Bong Oh, Sang-Jip Nam and Dong-Chan Oh*, ","doi":"10.1021/acs.jnatprod.3c00993","DOIUrl":"10.1021/acs.jnatprod.3c00993","url":null,"abstract":"<p >Serratiomycin (<b>1</b>) is an antibacterial cyclic depsipeptide, first discovered from a <i>Eubacterium</i> culture in 1998. This compound was initially reported to contain <span>l</span>-Leu, <span>l</span>-Ser, <span>l</span>-<i>allo</i>-Thr, <span>d</span>-Phe, <span>d</span>-Ile, and hydroxydecanoic acid. In the present study, <b>1</b> and three new derivatives, serratiomycin D1–D3 (<b>2</b>–<b>4</b>), were isolated from a <i>Serratia</i> sp. strain isolated from the exoskeleton of a long-horned beetle. The planar structures of <b>1</b>–<b>4</b> were elucidated by using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Comparison of the NMR chemical shifts and the physicochemical data of <b>1</b> to those of previously reported serratiomycin indeed identified <b>1</b> as serratiomycin. The absolute configurations of the amino units in compounds <b>1</b>–<b>4</b> were determined by the advanced Marfey’s method, 2,3,4,6-tetra-<i>O</i>-acetyl-β-<span>d</span>-glucopyranosyl isothiocyanate derivatization, and liquid chromatography–mass spectrometric (LC–MS) analysis. Additionally, methanolysis and the modified Mosher’s method were used to determine the absolute configuration of (3<i>R</i>)-hydroxydecanoic acid in <b>1</b>. Consequently, the revised structure of <b>1</b> was found to possess <span>d</span>-Leu, <span>l</span>-Ser, <span>l</span>-Thr, <span>d</span>-Phe, <span>l</span>-<i>allo</i>-Ile, and <span>d</span>-hydroxydecanoic acid. In comparison with the previously published structure of serratiomycin, <span>l</span>-Leu, <span>l</span>-<i>allo</i>-Thr, and <span>d</span>-Ile in serratiomycin were revised to <span>d</span>-Leu, <span>l</span>-Thr, and <span>l</span>-<i>allo</i>-Ile. The new members of the serratiomycin family, compounds <b>2</b> and <b>3</b>, showed considerably higher antibacterial activities against <i>Staphylococcus aureus</i> and <i>Salmonella enterica</i> than compound <b>1</b>.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (1 and 2) and four known (3–6) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus Arthrinium arundinis. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (alt) for alternapyrones was identified from A. arundinis ZSDS-F3 and validated by heterologous expression in Aspergillus nidulans A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2′ could convert the methyl group 26-CH3 to a carboxyl group to produce 4 from 3. Another cytochrome P450 monooxygenase, Alt3′, catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce 1, 2, 5, and 6 from 4. Alternapyrone G (1) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer’s disease drug discovery.
{"title":"Anti-inflammatory and Neuroprotective α-Pyrones from a Marine-Derived Strain of the Fungus Arthrinium arundinis and Their Heterologous Expression","authors":"Yiwei Hu, Xiaoyang Zhao, Yue Song, Jiahui Jiang, Ting Long, Mengjing Cong, Yuhua Miao, Yonghong Liu, Zhiyou Yang, Yiguang Zhu, Junfeng Wang","doi":"10.1021/acs.jnatprod.4c00393","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00393","url":null,"abstract":"Fungal linear polyketides, such as α-pyrones with a 6-alkenyl chain, have been a rich source of biologically active compounds. Two new (<b>1</b> and <b>2</b>) and four known (<b>3</b>–<b>6</b>) 6-alkenylpyrone polyketides were isolated from a marine-derived strain of the fungus <i>Arthrinium arundinis</i>. Their structures were determined based on extensive spectroscopic analysis. The biosynthetic gene cluster (<i>alt</i>) for alternapyrones was identified from <i>A. arundinis</i> ZSDS-F3 and validated by heterologous expression in <i>Aspergillus nidulans</i> A1145 ΔSTΔEM, which revealed that the cytochrome P450 monooxygenase Alt2′ could convert the methyl group 26-CH<sub>3</sub> to a carboxyl group to produce <b>4</b> from <b>3</b>. Another cytochrome P450 monooxygenase, Alt3′, catalyzed successive hydroxylation, epoxidation, and oxidation steps to produce <b>1</b>, <b>2</b>, <b>5</b>, and <b>6</b> from <b>4</b>. Alternapyrone G (<b>1</b>) not only suppressed M1 polarization in lipopolysaccharide (LPS)-stimulated BV2 microglia but also stimulated dendrite regeneration and neuronal survival after Aβ treatment, suggesting alternapyrone G may be utilized as a privileged scaffold for Alzheimer’s disease drug discovery.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140832200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1021/acs.jnatprod.4c00231
Shu-Xi Jing, Connor M. McDermott, Parker L. Flanders, Mariana Reis-Havlat, Shao-Nong Chen, Ana K. Bedran-Russo, James B. McAlpine, Elizabeth A. Ambrose and Guido F. Pauli*,
In nature, proanthocyanidins (PACs) with A-type linkages are relatively rare, likely due to biosynthetic constraints in the formation of additional ether bonds to be introduced into the more common B-type precursors. However, A-type linkages confer greater structural rigidity on PACs than do B-type linkages. Prior investigations into the structure–activity relationships (SAR) describing how plant-derived PACs with B- and complex AB-type linkages affect their capacity for dentin biomodification indicate that a higher ratio of double linkages leads to a greater interaction with dentin type I collagen. Thus, A-type PACs emerge as particularly intriguing candidates for interventional functional biomaterials. This study employed a free-radical-mediated oxidation using DPPH to transform trimeric and tetrameric B-type PACs, 2 and 4, respectively, into their exclusively A-type linked analogues, 3 and 5, respectively. The structures and absolute configurations of the semisynthetic products, including the new all-A-type tetramer 5, were determined by comprehensive spectroscopic analysis. Additionally, molecular modeling investigated the conformational characteristics of all trimers and tetramers, 1–5. Our findings suggest that the specific interflavan linkages significantly impact the flexibility and low-energy conformations of the connected monomeric units, which conversely can affect the bioactive conformations relevant for dentin biomodification.
在自然界中,具有 A 型连接的原花青素(PAC)相对罕见,这可能是由于生物合成过程中需要在更常见的 B 型前体中引入额外的醚键。然而,与 B 型连接相比,A 型连接赋予 PAC 更大的结构刚性。之前对具有 B 型和复杂 AB 型连接的植物源 PAC 如何影响其牙本质生物改性能力的结构-活性关系(SAR)进行的研究表明,双连接的比例越高,与牙本质 I 型胶原的相互作用就越大。因此,A 型 PAC 成为介入性功能生物材料中特别令人感兴趣的候选材料。本研究利用自由基介导的 DPPH 氧化作用,将三聚体和四聚体的 B 型 PAC(分别为 2 和 4)分别转化为纯 A 型连接的类似物(分别为 3 和 5)。通过综合光谱分析确定了半合成产物(包括新的全 A 型四聚体 5)的结构和绝对构型。此外,分子建模研究了所有三聚体和四聚体 1-5 的构象特征。我们的研究结果表明,特定的黄烷间连接会显著影响连接单体单元的灵活性和低能构象,而这反过来又会影响与牙本质生物改性相关的生物活性构象。
{"title":"Chemical Transformation of B- to A-type Proanthocyanidins and 3D Structural Implications","authors":"Shu-Xi Jing, Connor M. McDermott, Parker L. Flanders, Mariana Reis-Havlat, Shao-Nong Chen, Ana K. Bedran-Russo, James B. McAlpine, Elizabeth A. Ambrose and Guido F. Pauli*, ","doi":"10.1021/acs.jnatprod.4c00231","DOIUrl":"10.1021/acs.jnatprod.4c00231","url":null,"abstract":"<p >In nature, proanthocyanidins (PACs) with A-type linkages are relatively rare, likely due to biosynthetic constraints in the formation of additional ether bonds to be introduced into the more common B-type precursors. However, A-type linkages confer greater structural rigidity on PACs than do B-type linkages. Prior investigations into the structure–activity relationships (SAR) describing how plant-derived PACs with B- and complex AB-type linkages affect their capacity for dentin biomodification indicate that a higher ratio of double linkages leads to a greater interaction with dentin type I collagen. Thus, A-type PACs emerge as particularly intriguing candidates for interventional functional biomaterials. This study employed a free-radical-mediated oxidation using DPPH to transform trimeric and tetrameric B-type PACs, <b>2</b> and <b>4</b>, respectively, into their exclusively A-type linked analogues, <b>3</b> and <b>5</b>, respectively. The structures and absolute configurations of the semisynthetic products, including the new all-A-type tetramer <b>5</b>, were determined by comprehensive spectroscopic analysis. Additionally, molecular modeling investigated the conformational characteristics of all trimers and tetramers, <b>1</b>–<b>5</b>. Our findings suggest that the specific interflavan linkages significantly impact the flexibility and low-energy conformations of the connected monomeric units, which conversely can affect the bioactive conformations relevant for dentin biomodification.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1021/acs.jnatprod.4c00258
Anton Möllerke, and , Stefan Schulz*,
Collembola are closely related to insects, but our knowledge of their often unique chemistry is limited. Here we report the identification of the epicuticular lipid nitidane, representing a novel class of epicuticular lipids. Nitidane (4) is an irregular terpene consisting of seven isoprene units, made up of a diterpene core that is modified by a geranyl moiety that is itself prenylated. The observed [46+(22+11)1]-terpene structure has not been reported before.
{"title":"Nitidane: An Irregular Prenylated Diterpene from the Cuticle of the Springtail Heteromurus nitidus","authors":"Anton Möllerke, and , Stefan Schulz*, ","doi":"10.1021/acs.jnatprod.4c00258","DOIUrl":"10.1021/acs.jnatprod.4c00258","url":null,"abstract":"<p >Collembola are closely related to insects, but our knowledge of their often unique chemistry is limited. Here we report the identification of the epicuticular lipid nitidane, representing a novel class of epicuticular lipids. Nitidane (<b>4</b>) is an irregular terpene consisting of seven isoprene units, made up of a diterpene core that is modified by a geranyl moiety that is itself prenylated. The observed [4<sup>6</sup>+(2<sup>2</sup>+1<sup>1</sup>)<sup>1</sup>]-terpene structure has not been reported before.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jnatprod.4c00258","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140651978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A–D (1–4) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using the one strain–many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A (1) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B (2) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound 1 exhibited cytotoxic activity against NCI-H446 cells with an IC50 value of 4.1 μM. In addition, compound 1 displayed weak antibacterial activity toward Staphylococcus aureus with an MIC value of 32 μg/mL.
{"title":"Phenylhydrazone Alkaloids from the Deep-Sea Cold Seep Derived Fungus Talaromyces amestolkiae HDN21-0307","authors":"Jiajin Wu, Wenxue Wang, Yuhuan Yang, Mudassir Shah, Jixing Peng, Luning Zhou, Guojian Zhang, Qian Che, Jing Li, Tianjiao Zhu* and Dehai Li*, ","doi":"10.1021/acs.jnatprod.4c00132","DOIUrl":"10.1021/acs.jnatprod.4c00132","url":null,"abstract":"<p >Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A–D (<b>1</b>–<b>4</b>) were isolated from the deep-sea cold seep derived fungus <i>Talaromyces amestolkiae</i> HDN21-0307 using the one strain–many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A (<b>1</b>) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B (<b>2</b>) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound <b>1</b> exhibited cytotoxic activity against NCI-H446 cells with an IC<sub>50</sub> value of 4.1 μM. In addition, compound <b>1</b> displayed weak antibacterial activity toward <i>Staphylococcus aureus</i> with an MIC value of 32 μg/mL.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1021/acs.jnatprod.4c00013
Zhengyuan Li, Ling Chai, Zhenzhou Tang, Hongrui Zhu, Peiying Xue, Fan Sun, Houwen Lin, Yongjun Zhou* and Xiao Lin*,
A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (1–7) from Streptomyces conglobatus RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey’s method, Mosher’s analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC50 values ranging from 40 nM to 3.5 μM.
{"title":"Precursor-Directed Biosynthesis of Neoantimycin Derivatives with Selective Cytotoxicity","authors":"Zhengyuan Li, Ling Chai, Zhenzhou Tang, Hongrui Zhu, Peiying Xue, Fan Sun, Houwen Lin, Yongjun Zhou* and Xiao Lin*, ","doi":"10.1021/acs.jnatprod.4c00013","DOIUrl":"10.1021/acs.jnatprod.4c00013","url":null,"abstract":"<p >A precursor-directed biosynthesis approach led to the accumulation of seven new neoantimycin derivatives (<b>1</b>–<b>7</b>) from <i>Streptomyces conglobatus</i> RJ2. Structure elucidation was conducted using NMR and HRESIMS analysis, and the absolute configuration was determined by advanced Marfey’s method, Mosher’s analysis, and ECD analysis. The obtained compounds revealed selective and significant cytotoxicity, specifically against colorectal cancer cells bearing the K-ras mutation, with IC<sub>50</sub> values ranging from 40 nM to 3.5 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140653683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
cis-12-oxo-Phytodieneoic acid-α-monoglyceride (1) was isolated from Arabidopsis thaliana. The chemical structure of 1 was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the cis-OPDA moiety in 1 was determined by comparison of 1H NMR spectra and ECD measurements. With respect to the absolute configuration of the β-position of the glycerol backbone, the 2:3 ratio of (S) to (R) was determined by making ester-bonded derivatives with (R)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride and comparing 1H NMR spectra. Wounding stress did not increase endogenous levels of 1, and it was revealed 1 had an inhibitory effect of A. thaliana post germination growth. Notably, the endogenous amount of 1 was higher than the amounts of (+)-7-iso-jasmonic acid and (+)-cis-OPDA in intact plants. 1 also showed antimicrobial activity against Gram-positive bacteria, but jasmonic acid did not. It was also found that α-linolenic acid-α-monoglyceride was converted into 1 in the A. thaliana plant, which implied α-linolenic acid-α-monoglyceride was a biosynthetic intermediate of 1.
{"title":"Isolation and Structure Determination of cis-OPDA-α-Monoglyceride from Arabidopsis thaliana","authors":"Shotaro Hirota, Yusuke Ito, Shiro Inoue, Naoki Kitaoka, Tohru Taniguchi, Kenji Monde, Kosaku Takahashi and Hideyuki Matsuura*, ","doi":"10.1021/acs.jnatprod.3c01237","DOIUrl":"10.1021/acs.jnatprod.3c01237","url":null,"abstract":"<p ><i>cis</i>-12-oxo-Phytodieneoic acid-α-monoglyceride (<b>1</b>) was isolated from <i>Arabidopsis thaliana</i>. The chemical structure of <b>1</b> was elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by FDMS and HRFDMS data. The absolute configuration of the <i>cis</i>-OPDA moiety in <b>1</b> was determined by comparison of <sup>1</sup>H NMR spectra and ECD measurements. With respect to the absolute configuration of the β-position of the glycerol backbone, the 2:3 ratio of (<i>S</i>) to (<i>R</i>) was determined by making ester-bonded derivatives with (<i>R</i>)-(+)-α-methoxy-α-trifluoromethylphenylacetyl chloride and comparing <sup>1</sup>H NMR spectra. Wounding stress did not increase endogenous levels of <b>1</b>, and it was revealed <b>1</b> had an inhibitory effect of <i>A. thaliana</i> post germination growth. Notably, the endogenous amount of <b>1</b> was higher than the amounts of (+)-7-<i>iso</i>-jasmonic acid and (+)-<i>cis</i>-OPDA in intact plants. <b>1</b> also showed antimicrobial activity against Gram-positive bacteria, but jasmonic acid did not. It was also found that α-linolenic acid-α-monoglyceride was converted into <b>1</b> in the <i>A. thaliana</i> plant, which implied α-linolenic acid-α-monoglyceride was a biosynthetic intermediate of <b>1</b>.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1021/acs.jnatprod.4c00259
Islam A. Abdelhakim*, Yushi Futamura, Yukihiro Asami, Hideaki Hanaki, Naoko Kito, Sachiko Masuda, Arisa Shibata, Atsuya Muranaka, Hiroyuki Koshino, Ken Shirasu, Hiroyuki Osada, Jun Ishikawa and Shunji Takahashi*,
Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. Streptomyces antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics. In this study, the expression of a previously uncharacterized SARP protein, Syo_1.56, in Streptomyces sp. RK18-A0406 significantly enhanced the production of known antimycins and led to the discovery of 12 elasnins (1–12), 10 of which were novel. The absolute stereochemistry of elasnin A1 was assigned for the first time to be 6S. Unexpectedly, Syo_1.56 seems to function as a pleiotropic rather than cluster-specific SARP regulator, with the capability of co-regulating two distinct biosynthetic pathways, simultaneously. All isolated elasnins were active against wild-type and methicillin-resistant Staphylococcus aureus with IC50 values of 0.5–20 μg/mL, some of which (elasnins A1, B2, and C1 and proelasnins A1, and C1) demonstrated moderate to strong antimalarial activities against Plasmodium falciparum 3D7. Elasnins A1, B3, and C1 also showed in vitro inhibition of the metallo-β-lactamase responsible for the development of highly antibiotic-resistant bacterial strains.
{"title":"Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity","authors":"Islam A. Abdelhakim*, Yushi Futamura, Yukihiro Asami, Hideaki Hanaki, Naoko Kito, Sachiko Masuda, Arisa Shibata, Atsuya Muranaka, Hiroyuki Koshino, Ken Shirasu, Hiroyuki Osada, Jun Ishikawa and Shunji Takahashi*, ","doi":"10.1021/acs.jnatprod.4c00259","DOIUrl":"10.1021/acs.jnatprod.4c00259","url":null,"abstract":"<p >Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. <i>Streptomyces</i> antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics. In this study, the expression of a previously uncharacterized SARP protein, Syo_1.56, in <i>Streptomyces</i> sp. RK18-A0406 significantly enhanced the production of known antimycins and led to the discovery of 12 elasnins (<b>1</b>–<b>12</b>), 10 of which were novel. The absolute stereochemistry of elasnin A<sub>1</sub> was assigned for the first time to be 6<i>S</i>. Unexpectedly, Syo_1.56 seems to function as a pleiotropic rather than cluster-specific SARP regulator, with the capability of co-regulating two distinct biosynthetic pathways, simultaneously. All isolated elasnins were active against wild-type and methicillin-resistant <i>Staphylococcus aureus</i> with IC<sub>50</sub> values of 0.5–20 μg/mL, some of which (elasnins A<sub>1</sub>, B<sub>2</sub>, and C<sub>1</sub> and proelasnins A<sub>1</sub>, and C<sub>1</sub>) demonstrated moderate to strong antimalarial activities against <i>Plasmodium falciparum</i> 3D7. Elasnins A<sub>1</sub>, B<sub>3</sub>, and C<sub>1</sub> also showed <i>in vitro</i> inhibition of the metallo-β-lactamase responsible for the development of highly antibiotic-resistant bacterial strains.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140666960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}