Yukyung Choi, Yeongseo Kim, Jin Wook Cha, Gyu Sung Lee, Huong T Pham, Men Thi Ngo, Saegun Kim, Chung Sub Kim, Kyo Bin Kang
{"title":"Iodide Enhances the Production of Pseurotin D over Pseurotin A by Inverting the Preference for the S<sub>N</sub>2 versus the S<sub>N</sub>2' Product in the Final Nonenzymatic Step.","authors":"Yukyung Choi, Yeongseo Kim, Jin Wook Cha, Gyu Sung Lee, Huong T Pham, Men Thi Ngo, Saegun Kim, Chung Sub Kim, Kyo Bin Kang","doi":"10.1021/acs.jnatprod.4c01128","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01128","url":null,"abstract":"<p><p>Nonenzymatic reactions, though critical in natural product biosynthesis, are significantly challenging to control. Adding 3% NaI to the culture medium of <i>Penicillium janczewskii</i> significantly increased pseurotin D (<b>1</b>) production and decreased pseurotin A (<b>2</b>) production. Previously, <b>1</b> and <b>2</b> were suggested to be produced via a nonenzymatic reaction, where the epoxide at C-10 undergoes S<sub>N</sub>2 (<b>2</b>) or S<sub>N</sub>2' (<b>1</b>) reactions. We confirmed that <b>1</b> was isolated as a 1:1 mixture of C-13 epimers by spectral elucidation via CP3 analysis aided by selective excitation NMR methods, which supported that <b>1</b> was produced through a nonenzymatic S<sub>N</sub>2' reaction. We propose that NaI increased the ratio of <b>1</b> by causing steric hindrance at the C-11 position of the transient intermediate, which makes C-13 more preferred in the S<sub>N</sub>2/S<sub>N</sub>2' competition.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875488","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}
{"title":"The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector.","authors":"Tadeusz F Molinski","doi":"10.1021/acs.jnatprod.4c01295","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01295","url":null,"abstract":"<p><p>Marine sponge diterpenoid isonitriles are exceptional nitrogenous natural products that exhibit antiplasmodial activity. Their biosynthesis presents a biosynthetic puzzle: how do the elements of NC engage terpenyl carbocations in isoprenoid secondary metabolism, and what is the biosynthetic precursor of the NC group? Cyanoformic acid (NC-COOH, <b>B1</b>) is proposed as a plausible delivery vehicle of NC that resolves a paradox in the commonly held proposition that an inorganic cyanide anion, CN<sup>-</sup>, terminates terpenoid isonitrile (TI) biosynthesis. DFT calculations of NC-COOH and its conjugate base, cyanoformate, NC-COO<sup>-</sup> (<b>B2</b>), support high nucleophilicity at N and explain bond-forming constitutionality: attack at N and formation of an isonitrile over its nitrile isomer. TI biogenesis is compared to the cyanoformamide-containing ceratamines that arise from oxidation of a terminal <i>N</i>-Gly amide precursor. A unifying model links C-NC vs C-CN bond formation and places Gly at the center of both biosynthetic schemes.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862530","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}
Suling Xu, Nengfei Wang, Qingzhou Meng, Wenjie Ma, Huayue Li
{"title":"Metabologenomics-Driven Discovery of Nocardimicins from a Psychrophilic <i>Nocardia</i> sp. Strain.","authors":"Suling Xu, Nengfei Wang, Qingzhou Meng, Wenjie Ma, Huayue Li","doi":"10.1021/acs.jnatprod.4c01140","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01140","url":null,"abstract":"<p><p>A combined strategy of 2D-NMR-metabolomics-driven substructure tracking with genome mining led to the targeted discovery of 10 nocobactin-type lipopeptides (<b>1</b>-<b>10</b>) from the Arctic-derived phychrophillic <i>Nocardia</i> sp. L-016, among which <b>1</b>-<b>5</b> are new compounds, named nocardimicins S-W. The phenoxazole moiety in <b>1</b>-<b>10</b>, featuring unique NMR values and correlations, was used as a probe for tracking nocardimicin analogues. The structures of <b>1</b>-<b>5</b> were established based on extensive MS and NMR spectroscopic analyses. The biosynthesis of nocardimicins (<b>1</b>-<b>10</b>) in <i>Nocardia</i> sp. L-016 is proposed to be achieved by the <i>noc</i> biosynthetic gene cluster, which is composed of two sub-gene clusters (I and II) separated by a 228 kb region. Compounds <b>1</b>-<b>10</b> showed moderate inhibition against human cancer cell lines of HCT116 and HepG2 with IC<sub>50</sub> values in the range of 3.5-10.2 μM. This work provides an effective application of paired-omics technologies in the discovery of new natural products.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869273","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}
{"title":"Pyridoxal 5'-Phosphate (PLP)-Dependent β- and γ-Substitution Reactions Forming Nonproteinogenic Amino Acids in Natural Product Biosynthesis.","authors":"Taku Mizutani, Ikuro Abe","doi":"10.1021/acs.jnatprod.4c01226","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01226","url":null,"abstract":"<p><p>Living organisms synthesize various nonproteinogenic amino acids (NPAAs) as the building blocks of natural products. These NPAAs are often biosynthesized by pyridoxal 5'-phosphate (PLP)-dependent enzymes, which catalyze β- or γ- substitutions. These enzymes contribute to the structural diversification of NPAAs by installing new functional groups to amino acid side chains. Recent developments in genome mining have led to the identification of various PLP-dependent enzymes catalyzing β- or γ- substitutions, which form NPAAs in secondary metabolism. This short review summarizes recently investigated PLP-enzymes catalyzing β- or γ-substitutions in the biosynthesis of NPAAs by covering the literature published from 2015 through 2024.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862529","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}
Paola Rubiano-Buitrago, Ronald A White, Amy P Hastings, Frank C Schroeder, Anurag A Agrawal, Christophe Duplais
{"title":"Cardenolides in <i>Asclepias syriaca</i> Seeds: Exploring the Legacy of Tadeus Reichstein.","authors":"Paola Rubiano-Buitrago, Ronald A White, Amy P Hastings, Frank C Schroeder, Anurag A Agrawal, Christophe Duplais","doi":"10.1021/acs.jnatprod.4c00960","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00960","url":null,"abstract":"<p><p>The common milkweed <i>Asclepias syriaca</i> is widespread in North America and produces cardenolide toxins that deter herbivores by targeting the transmembrane enzyme Na<sup>+</sup>/K<sup>+</sup>-ATPase. In 1979, Nobel Laureate Tadeus Reichstein elucidated the structure of novel cardenolides isolated from <i>A. syriaca</i> roots and proposed structures for several other cardenolides that could not be confirmed. In this study, we investigate the cardenolide composition of <i>A. syriaca</i> seeds, focusing on their abundance and <i>in vitro</i> inhibitory potency on the sensitive porcine Na<sup>+</sup>/K<sup>+</sup>-ATPase and that of the highly resistant large milkweed bug, <i>Oncopeltus fasciatus</i>. We identify five previously unreported cardenolides (<b>1</b>-<b>5</b>), three of which are predominantly found in seeds, in addition to the known syrioside (<b>6</b>), aspecioside (<b>7</b>), and the 2-thiazoline ring-containing cardenolide labriformin (<b>8</b>). Glucopyranosyl-allomethylosyl-12-deoxy aspecioside (<b>5</b>) is distinguished by lack of oxidation at C-12, and compounds <b>2</b>, <b>3</b>, <b>6</b>, and <b>8</b> contain a rare 1,4-dioxane motif. Inhibitory efficacy of the isolated cardenolides for sensitive and resistant enzymes appears to be correlated. Finally, we confirmed the structure of compound <b>2</b>, originally proposed by Tadeus Reichstein, and are pleased to share his original 1979 handwritten manuscript.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845311","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}
{"title":"Breviane Spiroditerpenoids with Anti-inflammatory and Antiviral Activities from Deep-Sea-Derived Fungus <i>Penicillium</i> sp. F59.","authors":"Yinghui Lv, Wenping Song, Zongze Shao, Tianlei Ying, Bihong Hong, Wenjing Tian, Siwen Niu","doi":"10.1021/acs.jnatprod.4c00997","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00997","url":null,"abstract":"<p><p>Twelve new breviane spiroditerpenoids, namely, chrysobreviones A-L (<b>1</b>-<b>12</b>), together with seven structurally related analogues (<b>13</b>-<b>19</b>) were isolated from the EtOAc extract of the fermented cultures of deep-sea-derived fungus <i>Penicillium</i> sp. F59. These structures including absolute configurations were resolved on the basis of extensive analysis of NMR spectroscopic data and HRESIMS, in association with experimental and calculated ECD data as well as the modified Mosher's method. Compound <b>1</b> represented the first breviane derivative containing an unusual octahydrodifuro[2,3-b:2',3'-d]furan moiety, while <b>7</b> and <b>9</b> were the first breviones featuring an epoxy ring and an 18-hydroxymethyl group, respectively. The anti-inflammatory and antiviral activities of compounds <b>1</b>-<b>19</b> were evaluated. Compounds <b>1</b>, <b>8</b>, <b>16</b>, and <b>17</b> showed inhibitory effects against NO secretion in LPS-activated Raw264.7 macrophage cells with IC<sub>50</sub> values ranging from 1.4 to 12.9 μM, while <b>1</b> and <b>7</b> exhibited antiviral effects against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron subvariant BA.2 pseudovirus with IC<sub>50</sub> values of 8.5 and 10.3 μM, respectively.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833095","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}
{"title":"Chromones Featuring a [6,6]-Spiroketal Moiety Produced by Coculture of the Endophytic Fungi <i>Chaetomium virescens</i> and <i>Xylaria Grammica</i>.","authors":"Sitian Zhang, Nanjing Ding, Xinyu Zheng, Yuling Lu, Jiangchun Wei, Hanxiao Zeng, Weiguang Sun, Yuan Zhou, Ya Gao, Yonghui Zhang, Zhengxi Hu","doi":"10.1021/acs.jnatprod.4c00773","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00773","url":null,"abstract":"<p><p>Under the guidance of HPLC-DAD analysis, ten new chromones featuring a rare [6,6]-spiroketal moiety, namely chaetovirexylariones A-J (<b>1</b>-<b>10</b>), together with two known congeners (<b>11</b>-<b>12</b>), were isolated from coculture of the endophytic fungi <i>Chaetomium virescens</i> and <i>Xylaria grammica</i>, from the rhizome of the medicinal plant <i>Smilax glabra</i> Roxb. Their structures were elucidated via a combination of NMR and HRESIMS data, and the absolute configurations of <b>1</b>-<b>10</b> were determined by the chemical conversion and single-crystal X-ray diffraction (Cu Kα) experiments, as well as the comparison of the experimental and calculated electronic circular dichroism (ECD) data. Compound <b>6</b> is the first report as a racemate of this type of natural product. Compound <b>10</b> represents the first example of a [6,6]-spiroketal chromone bearing a 5-amino-3-methyl-2-pentenoic acid fragment. Compound <b>8</b> demonstrated a reduction in PTX resistance of SW620/AD300 by a factor of 45, and had the potential to be an effective P-gp inhibitor and an antitumor chemotherapy sensitizer.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833102","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}
Nirmal K Chaudhary, Daniel Vuong, Ernest Lacey, Andrew M Piggott, Peter Karuso
{"title":"Phenalenones and Polyesters from <i>Talaromyces stipitatus</i> and Structure Revision of Talaromycesone A.","authors":"Nirmal K Chaudhary, Daniel Vuong, Ernest Lacey, Andrew M Piggott, Peter Karuso","doi":"10.1021/acs.jnatprod.4c00885","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00885","url":null,"abstract":"<p><p>Investigation of the secondary metabolites of the filamentous fungus <i>Talaromyces stipitatus</i> led to the isolation of two new phenalenone dimers, talarohemiketal A (<b>1</b>) and talaroazasone A (<b>2</b>), and one new macrolide polyester, talaromacrolactone A (<b>3</b>), along with the reported oxyphenalenone dimers talaromycesone A (<b>4</b>), bacillisporin A (<b>5</b>), bacillisporin B (<b>6</b>), bacillisporin C (<b>7</b>), <i>epi</i>-bacillisporin F (<b>8</b>), and bacillisporin J (<b>9</b>), the phenalenone monomer funalenone (<b>10</b>), the polyesters 15G256α (<b>11</b>) and 15G256ν (<b>12</b>), and 6-hydroxymellein (<b>13</b>). Detailed analysis of 2D NMR correlations, supported by TDDFT calculations, led to the structural revision of talaromycesone A as <b>4</b> from previously reported structure <b>14</b>. In addition, the previously misassigned NMR spectra of compound <b>8</b> have been corrected.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833106","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}
Katarzyna Pokajewicz, Tomasz Biernat, Piotr P Wieczorek
{"title":"Is Linalyl Anthranilate Indeed Found In Plant Samples? GC-MS Misidentifications in the Scientific Literature.","authors":"Katarzyna Pokajewicz, Tomasz Biernat, Piotr P Wieczorek","doi":"10.1021/acs.jnatprod.4c01118","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01118","url":null,"abstract":"<p><p>Linalyl anthranilate (LNA) has been identified in a number of plant extracts and essential oils by various authors using gas chromatography-mass spectrometry (GC-MS). However, the reported retention behavior of LNA in these studies is inconsistent with the retention data provided in the NIST database. Therefore, the objective of this study was to determine whether the reports of LNA were the result of misidentifications in GC-MS analyses or if the linear NIST retention index was inaccurate. To accomplish this, linalyl anthranilate was synthesized in a two-step procedure, and the resulting product was authenticated using nuclear magnetic resonance (NMR) and GC-MS analyses. This is a new synthetic route to linalyl anthranilate. Subsequently, retention indices for linalyl anthranilate were determined on three commonly used GC phases: polydimethylsiloxane, 5% diphenyl-95% polydimethylsiloxane, and polyethylene glycol. The study confirmed the accuracy of the NIST retention data, establishing the linear retention index data for LNA on a semi-nonpolar GC column as 2051. However, LNA reported in the literature by various authors exhibited a retention index in the elution window of approximately 1000-1400, strongly suggesting that these reports were the result of GC-MS misidentifications. A review of all reported occurrences of LNA in natural samples found no credible evidence of its presence. In many cases, it appears to be a misidentification of linalyl acetate caused by the occurrence of an erroneous spectrum in the older versions of the NIST mass spectra database.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833104","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}
Joon Soo An, Jung Min Kim, Jaeho Han, Jun Young Lee, Sang-Jip Nam, Sang Kook Lee, Yeo Joon Yoon, Dong-Chan Oh
{"title":"Discovery of Cyclic Lipopeptides, Octaminomycins C and D, by Engineering LysR Transcriptional Regulator of <i>Streptomyces</i> sp.","authors":"Joon Soo An, Jung Min Kim, Jaeho Han, Jun Young Lee, Sang-Jip Nam, Sang Kook Lee, Yeo Joon Yoon, Dong-Chan Oh","doi":"10.1021/acs.jnatprod.4c01047","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01047","url":null,"abstract":"<p><p>New lipodepsipeptides, octaminomycins C and D (<b>1</b> and <b>2</b>), were discovered in an engineered <i>Streptomyces</i> sp. strain overexpressing the LysR transcriptional regulator family. The structures of <b>1</b> and <b>2</b> were elucidated by comprehensive analysis of their UV, HRMS, and NMR data. The absolute configurations were determined using spectroscopic analysis, the advanced Marfey's method, and genomic analysis. Genomic analysis enabled the identification of the nonribosomal peptide synthetase (NRPS) biosynthetic pathway of the octaminomycins.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816771","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}