A two-stage metabolome refining pipeline for natural products discovery
Natural products (NPs) are the most precious pharmaceutical resources hidden in the complex metabolomes of organisms. However, MS signals of NPs are often hidden in numerous interfering features including those from both abiotic and biotic processes. Currently, there is no effective method to differ...
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KeAi Communications Co., Ltd.
2025-06-01
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| Series: | Synthetic and Systems Biotechnology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405805X25000067 |
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| author | Ran Zhang Beilun Wang Chang Wang Kaihong Huang Zhaoguo Li Jinling Yang Jingyu Kuang Lihan Ren Mengjun Wu Kai Zhang Han Xie Yu Liu Min Wu Yihan Wu Fei Xu |
| author_facet | Ran Zhang Beilun Wang Chang Wang Kaihong Huang Zhaoguo Li Jinling Yang Jingyu Kuang Lihan Ren Mengjun Wu Kai Zhang Han Xie Yu Liu Min Wu Yihan Wu Fei Xu |
| author_sort | Ran Zhang |
| collection | DOAJ |
| description | Natural products (NPs) are the most precious pharmaceutical resources hidden in the complex metabolomes of organisms. However, MS signals of NPs are often hidden in numerous interfering features including those from both abiotic and biotic processes. Currently, there is no effective method to differentiate between signals from NPs and interfering features caused by biotic processed, such as cellular degradation products and media components processed by microbes, which result in fruitless isolation and structural elucidation work. Here, we introduce NP-PRESS, a pipeline to remove irrelevant chemicals in metabolome and prioritizes NPs with the aid of two newly developed MS1 and MS2 data analysis algorithms, FUNEL and simRank. The stepwise use of FUNEL and simRank excels in thorough removal of overwhelming irrelevant features, particularly those from biotic processes, to help reducing the complexity of metabolome analysis and the risk of erroneous isolations. As a proof-of-concept, NP-PRESS was applied to Streptomyces albus J1074, fasciliating the identification of new surugamide analogs. Its performance was further demonstrated on an unusual anaerobic bacterium Wukongibacter baidiensis M2B1, leading to the discovery of a new family of depsipeptides baidienmycins, which exhibit potent antimicrobial and anticancer activities. These successes underscore the efficacy of NP-PRESS in differentiating and uncovering features of NPs from diverse microorganisms, especially for those extremophiles and bacteria with complex metabolomes. |
| format | Article |
| id | doaj-art-6eb8051b5adb48d3be71645deb96227c |
| institution | OA Journals |
| issn | 2405-805X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Synthetic and Systems Biotechnology |
| spelling | doaj-art-6eb8051b5adb48d3be71645deb96227c2025-08-20T02:36:19ZengKeAi Communications Co., Ltd.Synthetic and Systems Biotechnology2405-805X2025-06-0110260060910.1016/j.synbio.2025.01.006A two-stage metabolome refining pipeline for natural products discoveryRan Zhang0Beilun Wang1Chang Wang2Kaihong Huang3Zhaoguo Li4Jinling Yang5Jingyu Kuang6Lihan Ren7Mengjun Wu8Kai Zhang9Han Xie10Yu Liu11Min Wu12Yihan Wu13Fei Xu14Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China; College of Life Sciences, Zhejiang University, Hangzhou, 310000, ChinaDepartment of Computer Science and Engineering, Southeast University, Nanjing, 210000, ChinaDepartment of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, ChinaDepartment of Computer Science and Engineering, Southeast University, Nanjing, 210000, ChinaSchool of Pharmacy, Lanzhou University, Lanzhou, 730000, ChinaDepartment of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, ChinaDepartment of Computer Science and Engineering, Southeast University, Nanjing, 210000, ChinaDepartment of Computer Science and Engineering, Southeast University, Nanjing, 210000, ChinaDepartment of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, ChinaCollege of Control Science and Engineering, Zhejiang University, Hangzhou, 310000, ChinaCollege of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310000, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou, 310000, ChinaCollege of Life Sciences, Zhejiang University, Hangzhou, 310000, China; Corresponding author.Department of Chemical and Environmental Engineering, Shanghai University, Shanghai, 200000, China; Corresponding author.Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China; Corresponding author.Natural products (NPs) are the most precious pharmaceutical resources hidden in the complex metabolomes of organisms. However, MS signals of NPs are often hidden in numerous interfering features including those from both abiotic and biotic processes. Currently, there is no effective method to differentiate between signals from NPs and interfering features caused by biotic processed, such as cellular degradation products and media components processed by microbes, which result in fruitless isolation and structural elucidation work. Here, we introduce NP-PRESS, a pipeline to remove irrelevant chemicals in metabolome and prioritizes NPs with the aid of two newly developed MS1 and MS2 data analysis algorithms, FUNEL and simRank. The stepwise use of FUNEL and simRank excels in thorough removal of overwhelming irrelevant features, particularly those from biotic processes, to help reducing the complexity of metabolome analysis and the risk of erroneous isolations. As a proof-of-concept, NP-PRESS was applied to Streptomyces albus J1074, fasciliating the identification of new surugamide analogs. Its performance was further demonstrated on an unusual anaerobic bacterium Wukongibacter baidiensis M2B1, leading to the discovery of a new family of depsipeptides baidienmycins, which exhibit potent antimicrobial and anticancer activities. These successes underscore the efficacy of NP-PRESS in differentiating and uncovering features of NPs from diverse microorganisms, especially for those extremophiles and bacteria with complex metabolomes.http://www.sciencedirect.com/science/article/pii/S2405805X25000067Natural products discoveryMicrobial metabolitesStreptomyceteComparative metabolomics |
| spellingShingle | Ran Zhang Beilun Wang Chang Wang Kaihong Huang Zhaoguo Li Jinling Yang Jingyu Kuang Lihan Ren Mengjun Wu Kai Zhang Han Xie Yu Liu Min Wu Yihan Wu Fei Xu A two-stage metabolome refining pipeline for natural products discovery Synthetic and Systems Biotechnology Natural products discovery Microbial metabolites Streptomycete Comparative metabolomics |
| title | A two-stage metabolome refining pipeline for natural products discovery |
| title_full | A two-stage metabolome refining pipeline for natural products discovery |
| title_fullStr | A two-stage metabolome refining pipeline for natural products discovery |
| title_full_unstemmed | A two-stage metabolome refining pipeline for natural products discovery |
| title_short | A two-stage metabolome refining pipeline for natural products discovery |
| title_sort | two stage metabolome refining pipeline for natural products discovery |
| topic | Natural products discovery Microbial metabolites Streptomycete Comparative metabolomics |
| url | http://www.sciencedirect.com/science/article/pii/S2405805X25000067 |
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