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Combination of combined-culture of Amycolatopsis sp. with Tsukamurella pulmonis and GNPS molecular networking reveals novel sulfur-containing cyclic lipopeptides thioamycolamides F–I

Abstract

A series of novel sulfur-containing cyclic lipopeptides named thioamycolamides F–I (14), with thiazoline, sulfoxide/sulfide, and fatty acid moieties, was discovered by applying GNPS molecular networking technology against combined-culture broth of Amycolatopsis sp. 26-4 and Tsukamurella pulmonis TP-B0596. Planar structural elucidation was accomplished by HRMS and 1D/2D NMR spectroscopic data analyses. The absolute configuration was determined by the highly sensitive advanced Marfey’s method developed by our group, electronic circular dichroism (ECD) spectroscopy, chemical synthesis, and Gaussian calculation. Moreover, compound 2 exhibited cytotoxicity against human cervix adenocarcinoma HeLa S3 cells with an IC50 of 24.0 μM.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (grant number 82404465), the Senior Talent Foundation of Jiangsu University (grant number 5501290012), the Jiangsu Provincial Double-Innovation Doctor Program (grant number JSSCBS0623), the Chugai Foundation for Innovative Drug Discovery Science: C-FINDs (grant number 2025-CF-01 to HK), a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (17H06401, 23H04882, and 24H00493, all awarded to HK), the Project for Promotion of Cancer Research and Therapeutic Evolution (24ama221540 and 25ama221540 to HK), and the Platform Project for Supporting Drug Discovery and Life Science Research (24ama121034 and 25ama121034 to HK) from the Japan Agency for Medical Research and Development (AMED), Japan.

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Correspondence to Hideaki Kakeya.

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Pan, C., Zhang, L., Kuranaga, T. et al. Combination of combined-culture of Amycolatopsis sp. with Tsukamurella pulmonis and GNPS molecular networking reveals novel sulfur-containing cyclic lipopeptides thioamycolamides F–I. J Antibiot 79, 293–300 (2026). https://doi.org/10.1038/s41429-026-00909-z

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