Journal of Natural Products 最新文献_第2页

Tailoring of Prematurely Released Polyketide Intermediates in Piericidin Biosynthesis. 吡虫啉生物合成中提前释放聚酮中间体的裁剪。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-27 DOI: 10.1021/acs.jnatprod.5c00609

Hattan A Alharbi, Muhammad Amin, Kh Ahammad Uz Zaman, Wei Zhou, Zhiran Ju, Taifo Mahmud

{"title":"Tailoring of Prematurely Released Polyketide Intermediates in Piericidin Biosynthesis.","authors":"Hattan A Alharbi, Muhammad Amin, Kh Ahammad Uz Zaman, Wei Zhou, Zhiran Ju, Taifo Mahmud","doi":"10.1021/acs.jnatprod.5c00609","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00609","url":null,"abstract":"Piericidins make up a group of microbial-derived polyketide natural products with a wide variety of biological activities. Their biosynthetic gene clusters (BGCs) have been identified in several strains of Streptomyces. In Streptomyces pactum, the piericidin BGC splits into two loci consisting of genes that encode six modular (type I) polyketide synthases and five post polyketide synthase (PKS) modification enzymes. Here, we report that inactivation of the pieA5 gene of the piericidin PKS in a mutant strain of S. pactum, in which several other major biosynthetic pathways have been inactivated, led to the identification of four piericidin polyketide intermediates (1-4) that were offloaded prematurely from the PKS. Compounds 1-3 are derived from an isopropyl starter unit, whereas compound 4 is derived from an acetyl starter unit. Compounds 1 and 4 have a terminal carboxylic acid, whereas compounds 2 and 3 have a terminal amide and a pendant methyl group at C-2. Compound 3 also contains an epoxide ring in the polyketide chain. The results reveal the ability of the piericidin PKS to offload incomplete polyketide intermediates and uncover the highly promiscuous tailoring enzymes that can modify the prematurely released short chain polyketides.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726009","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}

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Brodie W. Bulcock, Gavin R. Flematti and Samuele Sala*,

引用次数: 0

The Transcriptional Architecture of Bacterial Biosynthetic Gene Clusters. 细菌生物合成基因簇的转录结构。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-25 Epub Date: 2025-06-26 DOI: 10.1021/acs.jnatprod.5c00529

Silvia Ribeiro Monteiro, Yasmine Kerdel, Julianne Gathot, Sébastien Rigali

{"title":"The Transcriptional Architecture of Bacterial Biosynthetic Gene Clusters.","authors":"Silvia Ribeiro Monteiro, Yasmine Kerdel, Julianne Gathot, Sébastien Rigali","doi":"10.1021/acs.jnatprod.5c00529","DOIUrl":"10.1021/acs.jnatprod.5c00529","url":null,"abstract":"Bacterial biosynthetic gene clusters (BGCs) drive the production of diverse bioactive specialized metabolites regulated by transcription factors (TFs) in response to environmental signals. In this meta-analysis, we investigated the regulatory architecture of BGCs by compiling experimental data sets of transcription factor binding sites (TFBSs) to unveil (i) the functional gene categories preferentially targeted by TFs, (ii) the transcriptional coverage based on cluster organization, (iii) the positional distribution of TFBSs, and (iv) the binding strength of TFs. Our analysis reveals a strategy where global TFs primarily target monocistronic pathway-specific TFs when present, aligning with a \"one-for-all\" strategy ensuring cluster-wide expression control. In contrast, biosynthetic genes are typically organized into polycistronic operons, promoting the synchronized production of building blocks, core structures, and modifications. Assessment of the TF-TFBS interaction strength indicates that TFBSs within BGCs exhibit lower binding affinities compared to those associated with core regulon genes outside BGCs. This lower binding affinity allows greater regulatory flexibility, as BGC expression often responds to multiple environmental signals, each one sensed by its specific TF. These findings refine our understanding of the regulatory logic shaping BGC expression and offer valuable insights for predicting activation conditions, facilitating the discovery of novel compounds through targeted culture and engineering strategies.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1772-1780"},"PeriodicalIF":3.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144493169","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}

引用次数: 0

Metabolic Shunting in Marine-Derived Diaporthe sp. SYSU-MS4722 Yields Diverse γ-Butyrolactone Derivatives with Anti-inflammatory Activity. 海洋来源的Diaporthe sp. SYSU-MS4722代谢分流产生多种具有抗炎活性的γ-丁内酯衍生物。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-25 Epub Date: 2025-06-28 DOI: 10.1021/acs.jnatprod.5c00357

Siwen Yuan, Shitao Zhuang, Yongkang Qiao, Qilin Wu, Yutong Ma, Senhua Chen, Lan Liu, Yan Yan, Zhizeng Gao

{"title":"Metabolic Shunting in Marine-Derived Diaporthe sp. SYSU-MS4722 Yields Diverse γ-Butyrolactone Derivatives with Anti-inflammatory Activity.","authors":"Siwen Yuan, Shitao Zhuang, Yongkang Qiao, Qilin Wu, Yutong Ma, Senhua Chen, Lan Liu, Yan Yan, Zhizeng Gao","doi":"10.1021/acs.jnatprod.5c00357","DOIUrl":"10.1021/acs.jnatprod.5c00357","url":null,"abstract":"Filamentous fungi have significant potential to produce diverse secondary metabolites. However, the majority of fungal biosynthetic gene clusters (BGCs) remain cryptic under standard laboratory conditions, thereby limiting the chances of discovering novel metabolites. In our previous study, the marine fungus Diaporthe sp. SYSU-MS4722 was found to contain 130 BGCs, despite predominately producing phomoxanthone A and its analogues. By deleting the polyketide synthase gene phoE, which is responsible for the skeleton construction in the biosynthesis of phomoxanthone A, we successfully activated the metabolic shunting of Diaporthe sp. SYSU-MS4722, leading to the isolation of nine new γ-butyrolactone derivatives, colletolides C-K (1-9), along with known compound colletolide B (10). Their structures were elucidated by 1D and 2D NMR, modified Mosher's method, ECD calculations, and DP4+ probability analysis. All compounds were evaluated for anti-inflammatory activity by measuring IL-6 inhibition in A549 cells using ELISA. Compounds 1-9 exhibited anti-inflammatory activity, with EC50 values ranging from 24 to 106 μM. Among them, colletolide D (2) and colletolide B (10) showed the lowest EC50 values of 24 μM, indicating relatively stronger activity within this series. These findings indicate that colletolides D (2) and B (10) are promising lead compounds for anti-inflammatory drug development.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1605-1615"},"PeriodicalIF":3.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525462","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}

引用次数: 0

Insights into the Biosynthesis of Kibdelomycin and Amycolamicin from Comparative Biosynthetic Gene Cluster Analysis and Precursor Incorporation Studies. 从比较生物合成基因聚类分析和前体掺入研究对基德霉素和Amycolamicin生物合成的见解。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25 DOI: 10.1021/acs.jnatprod.5c00726

Marina Sánchez-Hidalgo, José Miguel Quesada, Daniel Oves-Costales, Jonah Fine, Jesús Martín, Fernando Román-Hurtado, Ryann Callaghan, Vanessa Raab, Jillian Scarpanito, John B Perkins, Neal Connors, Vincent Gullo, Ryan D Cohen, Benjamin Philmus, Sheo B Singh, Olga Genilloud

{"title":"Insights into the Biosynthesis of Kibdelomycin and Amycolamicin from Comparative Biosynthetic Gene Cluster Analysis and Precursor Incorporation Studies.","authors":"Marina Sánchez-Hidalgo, José Miguel Quesada, Daniel Oves-Costales, Jonah Fine, Jesús Martín, Fernando Román-Hurtado, Ryann Callaghan, Vanessa Raab, Jillian Scarpanito, John B Perkins, Neal Connors, Vincent Gullo, Ryan D Cohen, Benjamin Philmus, Sheo B Singh, Olga Genilloud","doi":"10.1021/acs.jnatprod.5c00726","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00726","url":null,"abstract":"Kibdelomycin and amycolamicin are identical antibiotics produced by Kibdelosporangium banguiense CA-240109 and Amycolatopsis sp. MK575-fF5, respectively. They are broad-spectrum antibiotics showing potent activity against antibiotic-resistant Gram-positive bacteria. These compounds inhibit DNA gyrase subunit B (GyrB) and topoisomerase IV (ParE) by a unique U-shaped multicontact binding mode and have no cross-resistance to known antibiotics. Kibdelomycin represents a promising scaffold for developing new antibiotics, but its poor production, structural complexity, and chemical stability limit its chemical modification. In this work, we describe the improvement of kibdelomycin production via strain mutagenesis and the elucidation of kibdelomycin biosynthesis using isotope-labeled feeding experiments and sequencing of the kibdelomycin and amycolamicin biosynthetic gene clusters (BGCs), which are similar but not identical. These studies provide avenues for structure-guided biosynthetic analogue development as well as material for chemical modification.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705771","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}

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Ángel D. Hernández-Mejías, Gabriel D. Jimenez-Nieves and Eduardo J. E. Caro-Diaz*,

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Caroline van Haaften*, Jan Koek, Jaap D. H. van Eendenburg, Jim van Wiltenburg, Daphne J. F. Kluitmans, Yvonne Grobben, Guido J. R. Zaman* and Wolter ten Hoeve,

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Shiwei Chen, Sarah Al Kinani, Oli Horyn, Colin Galliano, Era Srivastava, David C. Rowley, Kathryn M. Ramsey, Divita Mathur and Matthew J. Bertin*,

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Darren C. Holland, Reiko Iizumi, Vikram V. Shende* and William Fenical*,

引用次数: 0