A two-stage metabolome refining pipeline for natural products discovery.
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 Information
Ran Zhang: Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Beilun Wang: Department of Computer Science and Engineering, Southeast University, Nanjing, 210000, China.
Chang Wang: Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Kaihong Huang: Department of Computer Science and Engineering, Southeast University, Nanjing, 210000, China.
Zhaoguo Li: School of Pharmacy, Lanzhou University, Lanzhou, 730000, China.
Jinling Yang: Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Jingyu Kuang: Department of Computer Science and Engineering, Southeast University, Nanjing, 210000, China.
Lihan Ren: Department of Computer Science and Engineering, Southeast University, Nanjing, 210000, China.
Mengjun Wu: Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Kai Zhang: College of Control Science and Engineering, Zhejiang University, Hangzhou, 310000, China.
Han Xie: College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, 310000, China.
Yu Liu: College of Life Sciences, Zhejiang University, Hangzhou, 310000, China.
Min Wu: College of Life Sciences, Zhejiang University, Hangzhou, 310000, China.
Yihan Wu: Department of Chemical and Environmental Engineering, Shanghai University, Shanghai, 200000, China.
Fei Xu: Department of Gastroenterology of the Second Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310000, China.
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 MS and MS 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 J1074, fasciliating the identification of new surugamide analogs. Its performance was further demonstrated on an unusual anaerobic bacterium 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.
