Metabolomic Characterization of a cf. <i>Neolyngbya</i> Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells
Lijian Ding,
Rinat Bar-Shalom,
Dikla Aharonovich,
Naoaki Kurisawa,
Gaurav Patial,
Shuang Li,
Shan He,
Xiaojun Yan,
Arihiro Iwasaki,
Kiyotake Suenaga,
Chengcong Zhu,
Haixi Luo,
Fuli Tian,
Fuad Fares,
C. Benjamin Naman,
Tal Luzzatto-Knaan
Affiliations
Lijian Ding
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Rinat Bar-Shalom
Department of Human Biology, Faculty of Life Sciences, University of Haifa, Haifa 31905, Israel
Dikla Aharonovich
Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Haifa 31905, Israel
Naoaki Kurisawa
Department of Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan
Gaurav Patial
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Shuang Li
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Shan He
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Xiaojun Yan
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Arihiro Iwasaki
Department of Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan
Kiyotake Suenaga
Department of Chemistry, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan
Chengcong Zhu
Key Laboratory of Medicinal and Edible Plant Resources of Hainan Province, Hainan Vocational University of Science and Technology, Haikou 571126, China
Haixi Luo
Key Laboratory of Medicinal and Edible Plant Resources of Hainan Province, Hainan Vocational University of Science and Technology, Haikou 571126, China
Fuli Tian
Key Laboratory of Medicinal and Edible Plant Resources of Hainan Province, Hainan Vocational University of Science and Technology, Haikou 571126, China
Fuad Fares
Department of Human Biology, Faculty of Life Sciences, University of Haifa, Haifa 31905, Israel
C. Benjamin Naman
Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, China
Tal Luzzatto-Knaan
Department of Marine Biology, Leon H. Charney School of Marine Sciences, University of Haifa, Haifa 31905, Israel
Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.
